Bilateral anophthalmia and esophageal atresia: report of a new patient and review of the literature.
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Abnormalities, Multiple↗
Biomedical subjects
Lewis Spitz
Publications and source records attributed to Lewis Spitz.
Management of pyopagus conjoined twins.
INTRODUCTION: Approximately 18% of conjoined twins (1 in 200,000 live births) are joined at the sacrum ("pyopagus"). As the joined structures are not life-threatening, there is generally a good prognosis, with time for investigation and planning of operative separation. CASE REPORT: This paper reports on the management of pyopagus twin girls, the first in the UK delivered at 36 weeks by Caesarean section. The diagnosis had been made by ultrasound at 12 weeks' and confirmed by MRI scan at 26 weeks' gestation. Each twin had wasting and weakness below one knee, but no deficit in the other leg. The perineum had two urethras but only one anus. One infant had a colostomy in the immediate neonatal period. With appropriate further imaging, surgery was planned in two stages. First, a balloon expander was inserted in the bridging area. At 3 months of age a team comprising Plastic, Paediatric and Neurosurgeons undertook the definitive separation. DISCUSSION: Details of the multidisciplinary planning, operative separation and follow-up of these two children will be discussed.
Female↗
Tyrosine nitration of carnitine palmitoyl transferase I during endotoxaemia in suckling rats.
Heart carnitine palmitoyl transferase I (CPTI) is inhibited in vivo during endotoxaemia and in vitro by peroxynitrite but the biochemical basis of this inhibition is not known. The aim of this study was to determine which isoform of CPT I is inhibited during endotoxaemia and whether the inhibition is due to increased tyrosine nitration. Cardiac mitochondria were isolated from endotoxaemic suckling rats. To determine whether M- or L-CPTI was inhibited, we carried out titrations with DNP-etomoxir-CoA. Slopes of the titration curves with DNP-etomoxir-CoA were no different between control and endotoxaemia, suggesting that M-CPTI was specifically inhibited. Immunoprecipitation was carried out using an anti-nitrotyrosine antibody. Immunoprecipitated proteins were identified by Western blotting with L- and M-CPTI specific antibodies. L-CPTI was nitrated both in control and in 2- and 6-h endotoxaemia mitochondria but there was no significant difference in the level of nitration. M-CPTI was also nitrated in control mitochondria but nitration was significantly increased at both 2- and 6-h endotoxaemia. Either 10 mM 3-nitrotyrosine plus 40 microg nitrated-albumin or 0.5 M dithionite, during immunoprecipitation, greatly decreased immunopositivity for M- and L-CPTI on WB. M-CPTI appears to be a novel target for peroxynitrite during endotoxaemia, which would alter myocardial substrate selection.
Acyl Coenzyme A↗
Melatonin protects from, but does not reverse, the effects of mediators of sepsis on liver bioenergetics.
BACKGROUND: Reactive oxygen species (ROS) have been reported to play a significant role in the pathogenesis of sepsis and liver dysfunction. In particular, neonates are at risk for sepsis and have less protection against oxidation. Melatonin has been reported to reduce the oxidative stress status in neonates with sepsis. Little is known about the effect of melatonin on liver bioenergetics. The aim of this study was to investigate the protective effect of melatonin on hepatocyte oxidative energy metabolism against hydrogen peroxide (H2O2), a free radical mediator of septic damage. METHODS: Hepatocytes were isolated from neonatal suckling rats (11-15 days old). The cells, respiring on palmitate, were exposed to H2O2 at the concentration of 2 mmol/l, melatonin alone at 1 micromol/l or 10 micromol/l, or H2O2 plus melatonin at each of the two concentrations. Oxygen consumption was measured polarographically. In subsequent experiments, melatonin was added after the hydrogen peroxide. RESULTS: Hydrogen peroxide significantly reduced hepatocyte oxygen consumption ( p<0.001), but melatonin added at the same time was able to prevent this effect ( p<0.001). However, melatonin at a low dose significantly inhibited hepatocyte oxygen consumption ( p<0.001), an effect which has not been previously described. When melatonin was added to cells after they had been exposed to hydrogen peroxide, a beneficial effect was not observed, indicating that melatonin is not able to reverse the effects of hydrogen peroxide. CONCLUSION: Melatonin has a protective effect on hepatocyte oxidative metabolism, improving mitochondrial function by counteracting oxidative stress.
Animals↗
Neonatal severe hyperparathyroidism: genotype/phenotype correlation and the use of pamidronate as rescue therapy.
UNLABELLED: Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant condition due to heterozygous loss of function calcium sensing receptor (CaSR) mutations. However, individuals who are homozygous for CaSR mutations have neonatal severe hyperparathyroidism (NSHPT), which unlike the relatively benign and asymptomatic FHH can be fatal without parathyroidectomy. We report three patients with NSHPT associated with marked hypercalcaemia and severe hyperparathyroidism with related skeletal demineralisation. We describe the novel use of intravenous pamidronate in NSHPT, to control severe hypercalcaemia in these patients prior to parathyroidectomy and in one individual as a rescue therapy to stabilise life-threatening demineralisation. Furthermore, a marked phenotypic heterogeneity was observed amongst four members from a large kindred with the same homozygous CaSR mutations: one patient would have died without parathyroidectomy in infancy; a second patient survived infancy but underwent parathyroidectomy in early childhood following severe symptomatic hypercalcaemic episodes; whilst the other two patients have survived to adolescence without parathyroidectomy. Additionally, in contrast to the literature these two individuals suffered minimal morbidity. CONCLUSION: We commend the short-term use of pamidronate in neonatal severe hyperparathyroidism to treat extreme hypercalcaemia and halt hyperparathyroid-driven skeletal demineralisation in preparation for parathyroidectomy. The remarkable degree of phenotypic variation demonstrated remains unexplained without functional studies; this variability highlights the challenge of treating this rare condition.
Antineoplastic Agents↗
Gastric transposition in children--a 21-year experience.
PURPOSE: The purpose of this study was to analyze the outcome in 173 children (104 M, 69 F) undergoing transposition since 1981. METHODS: The most common indications for esophageal replacement included failed repair of different varieties of esophageal atresia (127), caustic injury (23), and peptic strictures (8). A total of 81% of the patients were referred from other hospitals (50% from other countries). Age at operation ranged from 7 days to 17 years. The gastric transposition was performed using blunt mediastinal dissection only in 90 patients with an additional 81 patients undergoing lateral thoracotomy. The retrosternal position was used in 2 patients. RESULTS: There were no graft failures including those who had previously failed gastric tube or Scharlilike operations. Anastomotic leakage occurred in 12% (all but 1 resolved spontaneously). Anastomotic stricture requiring dilatation occurred in 19.6%. Half of these patients had previous caustic esophageal injury. There were 9 deaths in the group (5.2%). One death occurred intraoperatively, 5 in the early postoperative period, and there were 3 late deaths. In more than 90% of our patients, the outcome was considered good to excellent in terms of absence of swallowing difficulties or other gastrointestinal symptoms. Many, however, preferred to eat small frequent meals. Poor outcome was particularly associated with multiple previous attempts at esophageal salvage. There was no deterioration in the function of the gastric transposition in those patients followed up for more than 10 years. CONCLUSIONS: Gastric transposition for esophageal substitution is an acceptable procedure. It is attended by 5% mortality and a 12% leak rate. A total of 19.6% of the patients needed anastomotic dilatation for stricture. In the long term, good function has been maintained. Gastric transposition compares favorably with alternative methods of esophageal replacement.
Adolescent↗
Gastroenteric fistula complicating percutaneous endoscopic gastrostomy.
BACKGROUND: Gastroenteric fistula occurs in 2% to 3% of patients undergoing percutaneous endoscopic gastrostomy (PEG). The authors identified 12 children with this major complication. METHODS: A retrospective case note review was performed. RESULTS: Over a 5-year period, the complication rate for gastroenteric fistula was 3.5% (12 of 343 procedures). Presentation ranged from 1 day to 25 months post-PEG insertion. Eight patients presented with acute intestinal obstruction. The gastroenteric fistulous tract involved the posterior wall of the stomach in all cases. The plain abdominal x-ray was useful in establishing the diagnosis of the gastroenteric fistula. CONCLUSIONS: Patients with gastroenteric fistula as a complication of PEG insertion can remain asymptomatic for prolonged periods. It often is difficult to make the diagnosis. A plain abdominal x-ray is a useful diagnostic modality.
Cerebral Palsy↗
Cloacal exstrophy: morbidity associated with abnormalities of the gastrointestinal tract and spine.
BACKGROUND/PURPOSE: The aim of this study was to review the management of the gastrointestinal tract in cloacal exstrophy and to assess the effect of spinal dysraphism on nutritional outcome. METHODS: Twenty-two patients with cloacal exstrophy were reviewed retrospectively. Gastrointestinal and spinal anomalies were documented. The need for nutritional supplementation was recorded. Weights at 1 and 5 years of age were used to assess growth in childhood. RESULTS: Ten patients were treated initially with ileostomy, 7 with colostomy, and 3 without stoma. Two patients died before surgical reconstruction. Total parenteral nutrition (TPN) was utilized in 8 infants for a median of 10 days (range, 5 to 200). Three patients had complications with colostomies requiring conversion to ileostomy. Patients with an ileostomy required more nutritional supplementation compared with patients with a colostomy (50% v 28%). High-output stoma losses were more common in patients with an ileostomy (40% v 14%). Fourteen patients (67%) with spinal dysraphism had a higher incidence of failure to thrive in the first year of life (69% v 26%) and multiple episodes of enteritis (40% v 25%). Two neonates with duodenal atresia and small bowel deletion died within the first month of life. One patient with short bowel syndrome died of TPN-associated liver disease at 6 months of age. There were no other deaths. CONCLUSIONS: The gastrointestinal tract contributes significantly to the morbidity and mortality in cloacal exstrophy. Nutritional supplementation is more frequently required in patients with an ileostomy. Stoma complications were higher in those with a colostomy. Morbidity is high in patients with spinal dysraphism.
Abnormalities, Multiple↗
Neonatal endotoxemia affects heart but not kidney bioenergetics.
PURPOSE: The aim was to determine the effects of early and late endotoxemia on neonatal cardiac and renal mitochondrial energetics. METHODS: Suckling rats received intraperitoneal 300 microgram/kg lipopolysaccharide; controls received saline. Heart and kidney mitochondria were isolated after 2 hours (early) or 6 hours (late sepsis). State 3 (maximum mitochondrial flux) and 4 O(2) consumption and complex I activity were measured. Results, expressed as mean +/- SEM normalized to citrate synthase (CS), were compared using paired t tests. RESULTS: Mortality rate was zero within 2 hours, 2.7% between 2 and 6 hours of endotoxemia, and 100% 6 to 8 hours; therefore, we consider that 2 hours and 6 hours represent early and late endotoxemia, respectively. Endotoxic heart mitochondria had unaltered O(2) consumption at 2 hours but significantly decreased state 3 after 6 hours, resulting in significantly decreased respiratory control ratio. Complex I activity, which could affect O(2) consumption, was decreased significantly at 6 hours (9.8 +/- 0.6 mU/U CS; n = 15) versus controls (11.3 +/- 0.8, n = 15; P =.04), but not at 2 hours. There were no differences in these measurements at either 2 hours or 6 hours in kidney mitochondria. CONCLUSIONS: The respiratory chain is affected late in endotoxemia. Neither early nor late endotoxemia affects oxidative function of kidney mitochondria.
Animals↗
Cardiac and renal mitochondria respond differently to hydrogen peroxide in suckling rats.
BACKGROUND: Overwhelming septicemia with multiple organ failure is one of the main causes of mortality with neonatal surgery. Liver, kidney, and heart are organs for which oxidative metabolism is particularly important. Hydrogen peroxide (H(2)O(2)), a major mediator of sepsis, inhibits liver metabolism. Our aim was to determine the effects of H(2)O(2) on neonatal renal and cardiac oxidative metabolism. MATERIALS AND METHODS: Mitochondria were isolated from the heart and kidney of 11 to 15-day-old rats. Oxygen consumption was measured polarographically in mitochondria incubated with different concentrations of H(2)O(2). State 3 oxygen consumption, which represents maximum mitochondrial oxidative flux, was measured in the presence of adenosine diphosphate. State 4 oxygen consumption, which represents oxygen consumption that is wasted and not used for adenosine triphosphate (ATP) generation, was measured after all adenosine diphosphate was used. beta-Oxidation flux and carnitine palmitoyltransferase I activity were measured radiochemically with increased levels of H(2)O(2). RESULTS: H(2)O(2) impaired state 3 oxygen consumption at all concentrations tested in cardiac and renal mitochondria. H(2)O(2) had no significant effect on heart mitochondrial state 4 oxygen consumption but significantly increased that of kidney. Heart, but not kidney, beta-oxidation flux was inhibited by H(2)O(2). Neither cardiac nor renal carnitine palmitoyltransferase I activity was affected by H(2)O(2). CONCLUSIONS: H(2)O(2) inhibits maximal rates of ATP generation by heart and kidney mitochondria but has a more severe effect on kidney mitochondria because more oxygen is wasted and not used for ATP generation. This decrease in ATP generation may be a factor in the dysfunction of these organs during sepsis.
Adenosine Triphosphate↗
Surgery of persistent hyperinsulinaemic hypoglycaemia.
Hyperinsulinism (HI) is the commonest cause of persistent or recurrent hypoglycaemia in childhood. HI is genetically and phenotypically diverse. Key management issues involve early diagnosis by insuring that appropriate investigations are undertaken at the point of hypoglycaemia, prevention of recurrent hypoglycaemia and clinical, biochemical and genetic characterisation of the HI syndrome. Children with persistent diazoxide resistant HI require investigation at specialist centres to differentiate those with a generalised disorder of the pancreas (diffuse HI; di-HI) from those with localised abnormalities within the pancreas (focal HI; fo-HI). Fo-HI may be managed by selective pancreatic resection of the focal abnormality. Di-HI is only managed by surgery if combination drug therapies are unable to prevent hypoglycaemia. Pancreatic beta-cell dysfunction persists following subtotal pancreatectomy of di-HI.
Decision Trees↗
Why parents of children with neurodevelopmental disabilities requiring gastrostomy feeding need more support.
This was a qualitative research study of parental perceptions of gastrostomy feeding before surgery using an in-depth interview in the parental home to examine the factors parents consider when gastrostomy feeding is recommended and to identify the need for support. Participants were a subgroup of families taking part in a larger research study evaluating gastrostomy placement in children with severe neurodevelopmental disabilities at a major paediatric centre in the UK between 1998 and 2000. Parents of 22 children (13 males, nine females; mean age 4 years 8 months [SD 3 years 6 months]; age range 1 year 1 month to 13 years 3 months) were interviewed. Categories of disability were: cerebral palsy (n=10), a syndrome of chromosomal or genetic origin (n=10), and unconfirmed diagnoses (n=2). Thirteen children were recommended for a gastrostomy and seven were recommended for a gastrostomy with an antireflux procedure. Four families were undecided about surgery at the time of the interview, two of whom went ahead with the procedure some time later. Parental accounts of oral and tube feeding were both contradictory and ambivalent. Concerns about the loss of oral feeding, which was regarded as having a range of psychosocial effects for the child and family, were raised. Both oral and tube feeding have multiple meanings for parents and signify more than obtaining an adequate nutritional intake. The need for additional information about the risks and benefits of gastrostomy and how tube feeding fits into the context of everyday life were dominant themes. The biomedical emphasis on health and weight-gains may fail to reflect parental concerns about tube and oral feeding. There is a need for greater practical and emotional support for families feeding children with severe disabilities.
Brain↗
Role of Sonic hedgehog in the development of the trachea and oesophagus.
BACKGROUND/PURPOSE: The secreted glycoprotein, Sonic hedgehog (Shh) plays an important patterning role in the development of many organ systems. The authors aimed to study the temporal and spatial pattern of expression of Shh and its receptor Ptc1 during the development of the anterior foregut and to test the hypothesis that the Shh expression pattern is disturbed during the development of oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF) in Adriamycin-treated mouse embryos. METHODS: Saline and Adriamycin-treated (4 mg/kg) CBA/Ca embryos were harvested between embryonic days (E) 10.5 and 12.5, and Shh and Ptc1 expression was studied by whole-mount and section in situ hybridisation using digoxygenin-labelled riboprobes. RESULTS: At E10.5, saline-treated embryos had an undivided foregut in which the ventrally placed prospective tracheal epithelium was positive for Shh, whereas the dorsal part was negative. At E11.5, this pattern had reversed with the separated trachea becoming negative and the oesophagus gaining expression of Shh. Ptc1 was expressed in the mesoderm adjacent to Shh expressing endoderm at both stages. Affected Adriamycin-treated embryos had an undivided foregut at E11.5, the epithelium of which showed diffuse Shh staining that lacked the dorso-ventral patterning seen in controls. CONCLUSIONS: The reversal in the dorso-ventral pattern of Shh expression during the narrow embryologic window in which tracheo-oesophageal separation is initiated suggests that Shh may play an important role in this process. Transient disturbance of this pattern may underlie the abnormal organogenesis in the Adriamycin model.
Animals↗
Body temperature and heat production in suckling rat endotoxaemia: beneficial effects of glutamine.
BACKGROUND/PURPOSE: Sepsis is an important cause of neonatal mortality. The aim of the study was to investigate the metabolism of endotoxic neonatal rats and the potential beneficial effect of glutamine. METHODS: Suckling rats received intraperitoneal saline (control; C), endotoxin (300 microg/g LPS; E), saline+glutamine (2 mmol/g; CG), endotoxin+glutamine (EG), saline+leucine (2 mmol/g; CL) or endotoxin+leucine (EL). Sepsis score (0-8) and rectal temperature were monitored. Hypothermia was defined as rectal temperature less than 32 degrees C. Oxygen consumption (VO2, mL/kg/h), a determinant of heat production, was measured by indirect calorimetry. Data (mean +/- SEM) were compared by analysis of variance (ANOVA), paired t test or Fisher's Exact test. RESULTS: Endotoxic (E) rats had significantly lower VO2 than C rats from 90 minutes postinjection to the end of the experiment, 210 minutes (VO2 from 150 to 210 minutes: C 671 +/- 45; E 429 +/- 36, P <.0004; n = 8; paired t test). VO2 of CL or CG rats was elevated between 90 and 210 minutes compared with control, but significantly (P <.01) only in the L group (C 706 +/- 31; CG 871 +/- 63; CL 984 +/- 31; n = 7-9, ANOVA). VO2 was significantly higher (P <.05) in EG rats than E rats (E 460 +/- 29; EG 654 +/- 68; n = 9-10). In the EL group, VO2 was raised but was not significantly different from E (E 460 +/- 29; EL 637 +/- 52; n = 8-10). EG rats were significantly less hypothermic between 90 and 210 minutes (58 of 132 measurements) compared with E (95 of 147; P =.0007, Fisher's Exact test), whereas the EL group were similarly hypothermic (74 of 120) to E (P =.7). Sepsis score was significantly lower in the EG group than both E and EL groups (E 4.9 +/- 0.3; EG 3.6 +/- 0.3; EL 5.0 +/- 0.3; n = 40; P <.01; ANOVA). CONCLUSIONS: Neonatal endotoxaemia lowers VO2, heat production, and body temperature. Glutamine and leucine both cause nutrient-induced thermogenesis in control animals and restore VO2 of endotoxic animals. Glutamine additionally increases rectal temperature, reduces incidence of hypothermia, and improves clinical signs of endotoxic rats. This suggests that glutamine may be beneficial for nutrition in neonatal sepsis.
Animals↗
Quality of life after gastric transposition for oesophageal atresia.
BACKGROUND/PURPOSE: A small proportion of infants born with oesophageal atresia in which the gap between the 2 ends of the oesophagus is too great for an end-to-end anastomosis will require oesophageal replacement. Since 1981 the author's procedure of choice for oesophageal replacement has been gastric transposition. The long-term functional outcome appears to be satisfactory, but the quality of life of these patients has not been investigated formally. This report assesses the health-related quality of life (QOL) of 2 groups of patients born with oesophageal atresia who have undergone gastric transposition. METHODS: The study group comprised 28 patients aged 2 to 22 years who resided in England. Group 1 (n = 13), comprised patients who had undergone cervical oesophagostomy and gastrostomy without attempt at oesophageal anastomosis; group 2 (n = 15), comprised patients who had undergone previous attempts at reconstruction or replacement. QOL was assessed using modified versions of the Gastrointestinal Quality Of Life Index (GIQLI). RESULTS: QOL scores based on patients' responses showed no significant differences between the groups (124 v 119). However, the disease-specific symptom scores showed that patients in group 1 experienced fewer symptoms compared with those in group 2. Additionally, based on parental responses, patients in group 1 had higher QOL scores than those in group 2. QOL scores for patients aged 2 to 4 years (n = 5) did not differ between the groups (81 v 92, not significant). CONCLUSIONS: The quality of life for patients with oesophageal atresia undergoing gastric transposition was generally unimpaired by any side effects of gastric transposition. Patients undergoing gastric transposition as a primary procedure experienced fewer disease-specific symptoms in the medium term compared with patients who had undergone previous unsuccessful attempts at reconstruction or replacement of their oesophagus.
Adolescent↗
Hypothermia throughout intestinal ischaemia-reperfusion injury attenuates lung neutrophil infiltration.
BACKGROUND/PURPOSE: Secondary organ damage to the lungs is an important consequence of intestinal ischaemia reperfusion (IIR) injury. Moderate hypothermia ameliorates gut necrosis and liver energy failure after IIR but potential beneficial effects on lung neutrophil infiltration after reperfusion of ischaemic bowel have not been investigated. METHODS: Adult Sprague-Dawley rats underwent 60 minutes intestinal ischaemia followed by 120 minutes of reperfusion. The animals were maintained at either normothermia (36 degrees to 38 degrees C) or moderate hypothermia (30 degrees to 32 degrees C). Four groups were studied: (A) sham normothermia; (B) IIR normothermia; (C) sham hypothermia; and (D) IIR hypothermia. Lungs and terminal ileum were removed for measurement of myeloperoxidase activity (a marker of neutrophil infiltration). Results are expressed as milliunits per milligrams protein, mean +/- SEM, and one-way analysis of variance (ANOVA) with Tukey post-test was used for group comparisons. RESULTS: Lungs: IIR at normothermia significantly increased lung neutrophil infiltration assessed by myeloperoxidase activity compared with sham-operated controls (normothermia sham 4.6 +/- 1.0, n = 8; normothermia IIR 37.7 +/- 13.8, n = 8; P =.011). Moderate hypothermia during IIR significantly attenuated lung neutrophil infiltration (7.2 +/- 2.1, n = 9) compared with normothermia IIR (P =.016) such that myeloperoxidase activity was similar to that found in sham normothermia (4.6 +/- 1.0, n = 8) and sham hypothermia (3.1 +/- 1.3, n = 8). Intestine: Gut myeloperoxidase activity was 0.9 +/- 0.5 in sham normothermia (n = 9) and 2.3 +/- 0.6 after normothermic IIR (n = 8). After IIR at hypothermia gut myeloperoxidase activity (0.5 +/- 0.2; n = 8) was significantly less than normothermic IIR (P =.035) and higher than sham hypothermia (0.2 +/- 0.1, n = 9; P =.01). CONCLUSIONS: These results indicate that moderate hypothermia may prevent damage to another distant organ, ie the lungs, by preventing recruitment of neutrophils. This may be of benefit in decreasing distal organ damage in diseases in which intestinal ischaemia-reperfusion is implicated in the pathogenesis.
Animals↗