Biomedical subjects
Publications and source records attributed to L Spitz.
The authors report the case of a 12-year-old boy with cystic fibrosis, in whom a percutaneous endoscopic gastrostomy device migrated into the jejunum, forming a gastrojejunal fistula.
BACKGROUND/PURPOSE: Studies in human surgical neonates have shown that intraoperative fentanyl analgesia results in greater fall in perioperative body core temperature compared with morphine analgesia. The aim of the study was to compare in a neonatal animal model the biochemical effect of fentanyl and morphine on hepatocyte oxidative metabolism. METHODS: Hepatocytes were isolated from suckling rats and the oxygen consumption from palmitate was measured polarographically. In experiment A, fentanyl and morphine within the respective analgesic serum ranges were added to hepatocytes to assess the effect on oxygen consumption. In experiment B, fentanyl was added to hepatocytes in the presence of inhibitors of mitochondrial respiration to investigate its site of action. In experiment C, hepatocytes were incubated with either fentanyl or morphine, centrifuged, and then examined ultrastructurally by electron microscopy. RESULTS: In experiment A, fentanyl inhibited oxygen consumption by up to 40% (P < .01). Morphine inhibited oxygen consumption to a maximum of 25% (P < .01). In experiment B, in the presence of oligomycin, fentanyl increased the inhibition of oxygen consumption; however, in the presence of myxothiazol, no further inhibition by fentanyl occurred. In experiment C, mild ultrastructural alterations to hepatocytes were observed after incubation with fentanyl but not with morphine. CONCLUSIONS: This study demonstrates that therapeutic doses of two commonly used analgesic drugs impair neonatal hepatic oxidative metabolism. Fentanyl exerts a greater effect than morphine by diminishing liver oxygen consumption by up to 40%. The inhibitory effect of fentanyl occurs directly on the mitochondrial respiratory chain, either on substrate oxidation or on the thermogenic proton leak. The findings of this study are relevant to the perioperative management of surgical neonates.
PURPOSE: The aim of this study was to evaluate the results of fundoplication performed in the first 4 months of life. METHODS: Case-notes of 66 patients less than 4 months old who underwent fundoplication between January 1986 and July 1997 were reviewed. The mean length of follow-up was 24 months (range, 3 to 115 months). Diagnosis of gastrooesophageal reflux (GOR) was based on a barium meal in 55 patients or 24-hour pH monitoring in 23 patients. RESULTS: Fundoplication was performed at a median age of 9 weeks (range, 3 to 15 weeks). Associated anomalies were identified in 56 infants and included oesophageal atresia or tracheooesophageal fistula (n = 19), lung abnormalities (n = 7), congenital diaphragmatic hernia (n = 4), and various other complex syndromes including neurological disorders (n = 26). Isolated GOR occurred in 10. Ninety percent of infants with isolated GOR improved clinically after the fundoplication compared with 64% of those with associated anomalies. Only 58% of infants in whom GOR developed after oesophageal atresia repair improved after fundoplication. Vomiting was reduced after fundoplication in 76% of infants, apnoea and/or respiratory symptoms improved in 66%, whereas failure to thrive incidence improved in only 38% of infants. Revision of the fundoplication was required in 16 (24%) patients. There were eight deaths, all of which occurred at least 6 months after the fundoplication. CONCLUSIONS: Fundoplication in early infancy is unsuccessful in a high proportion of patients. The highest incidence of failure and redo fundoplication occurred in infants with associated anomalies. The best results were achieved in infants with emesis and respiratory symptoms.
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.
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.
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.
PURPOSE: The aim of this study was to evaluate the results of surgical treatment of necrotizing enterocolitis (NEC) according to the extent of disease and to establish if resection of the ileocecal valve represents a poor prognostic factor. METHODS: The authors reviewed all cases of NEC (n = 161) treated in our hospital during the last 11 years; of these, 83 required surgical intervention. Definitions used by the authors include isolated, disease in a single intestinal segment; multifocal, disease in two or more intestinal segments; and pan-intestinal, majority of small and large bowel involved. RESULTS: Twenty-five neonates had isolated NEC, 46 neonates had multifocal NEC, and 12 had pan-intestinal involvement. Survival rate was affected by the extent of intestinal involvement, the lowest survival rate (33%) being noticed in neonates with pan-intestinal involvement. In patients with isolated NEC, postoperative complications and survival rate were not affected by the modality of operative treatment. Conversely, in patients with multifocal NEC, survival rate was higher (85%) after resection and primary anastomosis compared with enterostomy (50%; P =.03). Resection of the ileocecal valve was not associated with increased morbidity and mortality. CONCLUSIONS: (1) Resection and primary anastomosis is a valid treatment option in both isolated and multifocal NEC. (2) Neonates with NEC adapt rapidly to the loss of the ileocecal valve.
BACKGROUND/PURPOSE: Surgical neonates are at risk for sepsis and liver dysfunction. These complications are more common in preterm neonates and in those who receive total parenteral nutrition. Elevated levels of reactive oxygen species (eg, hydrogen peroxide) have been reported in these "at-risk" patients and may be the mediators of liver impairment via their effect on oxidative energy metabolism. The aim of this study was to test the hypothesis that elevated levels of hydrogen peroxide (H2O2) impair neonatal liver oxidative energy metabolism. METHODS: An in vitro model to test this hypothesis was developed in hepatocytes isolated from neonatal (11-day to 15-day) rats. The cells, respiring on palmitate (0.5 mmol/L in 2% bovine serum albumin), were exposed to H2O2. Oxygen consumption was measured polarographically. In experiment A, H2O2 was added to the cell preparation at different concentrations (0.5 mmol/L, 1 mmol/L, 1.5 mmol/L, 2 mmol/L) to assess the effect on oxygen consumption. In experiment B, H2O2 (2 mmol/L) was added to hepatocytes in the presence of inhibitors of mitochondrial respiration to define the site of action of H2O2. In experiment C, electron microscopy was performed on hepatocytes after incubation with 1 mmol/L and 2 mmol/L of H2O2. RESULTS: In experiment A, H2O2 significantly reduced hepatocyte oxygen consumption at 1.5 and 2 mmol/L. In experiment B, in the presence of inhibitors of mitochondrial respiration, myxothiazol (inhibitor of substrate oxidation), and oligomycin (inhibitor of adenosine triphosphate (ATP) synthase), no further inhibition by H2O2 occurred, indicating that the effect of H2O2 was intramitochondrial and affecting the synthesis of ATP. In experiment C, microscopic alterations of mitochondria were noticed exclusively in hepatocytes incubated with 2 mmol/L H2O2. CONCLUSIONS: Results of this study demonstrate that H2O2 impairs neonatal liver oxidative metabolism. H2O2 probably directly inhibits ATP synthase. The authors hypothesize that H2O2 may play a role in the biochemical pathogenesis of liver dysfunction associated with sepsis. Identification of the precise target site of H2O2 may be valuable in directing therapy in septic neonates.
BACKGROUND/PURPOSE: Conjoined twins often have different body composition and growth rate before separation. This may be because of differences in energy metabolism. The aim of this study was to investigate the energy expenditure, body composition, and calorie intake of thoracopagus conjoined twins with shared hepatic circulation but separate gastrointestinal tracts. METHODS: The twins were studied at two periods: (1) before separation (age, 73 days) and (2) after separation (age, 97 days). Calorie intake over the study periods was carefully documented. Respiratory gas exchange was measured by computerized indirect calorimetry. The postseparation weight ratio of twin A to twin B was used to approximate the preseparation weights. Body composition (total body fat) was calculated from skinfold thickness and anthropometric measurements. RESULTS: The body composition of the twins was different: body weight and total body fat were higher in twin B. Resting energy expenditure and calorie intake were markedly different between the conjoined twins before separation. In both twins, the energy expenditure increased after separation. After separation, the resting energy expenditure of the twins was similar. CONCLUSIONS: This study illustrates the difference in energy metabolism in a set of thoracopagus conjoined twins. The authors speculate that twin A was supplying nutrients to twin B resulting in increased energy expenditure before separation. This would explain the lower calorie intake and higher fat mass of twin B.
OBJECTIVE: To investigate the incidence of associated anomalies and document changes and progress in the management and outcome of intrinsic duodenal obstruction (atresia or stenosis) in a large series over a long time period with a view to providing comprehensive data for prenatal counselling. DESIGN: A retrospective casenote review. SETTING: A quaternary referral centre for paediatric and neonatal surgery. POPULATION: Two hundred and seventy-five infants born with duodenal obstruction between 1951 and 1995. METHODS: For analysis of management and outcome data, the series was divided into three groups, each admitted over 15 year periods: Group A, 1951-1965; Group B, 1966-1980; Group C, 1981-1995. MAIN OUTCOME MEASURES: Primary: associated anomalies, complication rates and survival. Secondary: age at diagnosis, duration of hospital stay. RESULTS: There were 136 males and 139 females. Seventeen of 30 cases (57%) presenting between 1991 and 1995 were diagnosed prenatally on ultrasound scan. The median age at diagnosis for atresia was 3.5 days (Group A); 2.2 days (Group B) and 1.8 days (Group C). The median age at diagnosis for incomplete obstruction was five days. Associated anomalies included Down's syndrome (n = 82, 30%); Down's plus cardiac malformation (n = 38, 14%); isolated cardiac (n = 64, 23%); and gastrointestinal problems (n = 116, 42%). Overall complication rates fell from 51% (Group A) to 18% (Group C) and survival increased from 51% to 95% . Median hospital stay also decreased from 35 days to 18 days. CONCLUSIONS: These data confirm a progressive improvement in the outcome of intrinsic duodenal obstruction over the past 45 years. It is important to note that they only relate to infants born with duodenal atresia and do not take into account possible 'hidden' mortality resulting from spontaneous abortion or termination.
AIMS: To document the long term course of chronic idiopathic intestinal pseudo-obstruction syndrome (CIIPS) in children with defined enteric neuromuscular disease, and the place and type of surgery used in their management; in addition, to identify prognostic factors. METHODS: Children with CIIPS were investigated and treated prospectively. RESULTS: Twenty four children presented congenitally, eight during the 1st year of life, and 10 later. Twenty two had myopathy and 16 neuropathy (11 familial). Malrotation was present in 16 patients, 10 had short small intestine, six had non-hypertrophic pyloric stenosis, and 16 had urinary tract involvement. Thirty two patients needed long term parenteral nutrition (TPN): for less than six months in 19 and for more than six months in 13, 10 of whom are TPN dependent; 14 are now enteral feeding. Prokinetic treatment improved six of 22. Intestinal decompression stomas were used in 36, colostomy relieved symptoms in five of 11, and ileostomy in 16 of 31. A poor outcome (death (14) or TPN dependence (10)) was seen with malrotation (13 of 16), short small bowel (eight of nine), urinary tract involvement (12 of 16), and myopathic histology (15 of 22). CONCLUSIONS: In CIIPS drugs are not helpful but decompression stomas are. Outcome was poor in 24 of 44 children (15 muscle disorder, 10 nerve disease).
Sacral agenesis is a heterogeneous group of congenital anomalies in which most cases are sporadic but rare familial forms also occur. Although one gene has been mapped to chromosome 7q36 in families with hemisacrum, associated with anorectal atresia and presacral mass, it is clear that the genetic aetiology of these disorders is complex and other genes remain to be discovered. Some years ago, the idea of T (Brachyury) as a candidate gene for sacral agenesis was raised, because tail abnormalities associated with T and the t complex, on mouse chromosome 17, resemble spinal defects seen in man. The recent cloning and mapping of the human T gene prompted us to re-evaluate this idea. T is a transcription factor essential for the normal development of posterior mesodermal structures. Although the sequence and function of T are highly conserved in evolution, our genetic study shows that the coding region of the human gene is highly polymorphic. Three common variable amino acid sites in known functional domains have been identified: Gly356Ser, Asn369Ser, and Gly177Asp. For the latter variant, functional studies have shown that the presence of Asp at residue 177 reduces the stability of T dimer formation. A search for rare mutation of T in 28 selected patients with sacral agenesis/anorectal atresia identified a novel, rare variant in one patient and her mother. This mutation leads to an amino acid change within a conserved activation domain. While the functional significance of this single mutation requires further investigation, we can conclude from our studies that if T has a role in the aetiology of sacral agenesis, its contribution is small in this particular set of patients. However, we cannot exclude a more major role in other forms of sacral defect.
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It has been assumed that only 10% of medical interventions are supported by solid scientific evidence. The aim of this study was to determine the type of research evidence supporting operations in a tertiary referral paediatric surgical unit. All patients admitted over a 4-week period to two surgical firms were enrolled in the study. All major operations carried out on each patient since birth were evaluated. Patients for whom a diagnosis was not reached were excluded. A bibliographic database (MEDLINE) was used to search for the articles published between January 1986 and December 1995 on the analysed operations. The type of evidence supporting the operations was classified as follows: I=evidence from randomised controlled trials (RCTs); II=self-evident intervention (obvious effectiveness not requiring RCTs); III=evidence from prospective and/or comparative studies; IV=evidence from follow-up studies and/or retrospective case series; and V=intervention without substantial evidence for or against results of randomised trials. Seventy operations (32 individual types) were performed on 49 patients (1-5 operations/patient); 18 (26%) were supported by RCTs (type of evidence I). Two patients (3%) received a self-evident intervention (type II); 48 operations (68%) were based on non-randomised prospective or retrospective studies (type III=13%; type IV=55%). Two patients (3%) received an operation not supported by or against convincing scientific evidence (type V). A significant proportion of operations in paediatric surgery is supported by RCTs. However, the vast majority of these trials were conducted on adult patients. Sixty-eight per cent of the operations were based on prospective follow-up studies or retrospective case series, which may not represent solid scientific evidence. More RCTs are needed in paediatric surgery.
Proteus syndrome is a multi-organ disorder, a prime feature of which is localized gigantism, usually clinically obvious. Symptoms secondary to hypertrophy of nerves has not been previously recognized as a part of the syndrome.
To analyse the clinical features and outcome following surgery of giant splenic cysts in children, all patients presenting to a children's hospital over the years 1987-1996 were reviewed. Variables analysed included presenting symptoms, method of diagnosis, operative procedure, and complications. Six patients (aged 8-16 years) presented with abdominal pain or a large abdominal mass. Ultrasound examination demonstrated large (>5 cm) unilocular splenic cysts. Five of the six children underwent hemisplenectomy without complication or blood transfusion. The remaining patient had an infected cyst, for which total splenectomy was necessary because of major intraoperative haemorrhage. Hemisplenectomy is based on accurate dissection of the splenic hilum with clear knowledge of the intracapsular vascular anatomy of the spleen. Preoperative vaccination is recommended in the event that splenectomy is required. This retrospective review concludes that hemisplenectomy for splenic cysts is a safe procedure in children.
PURPOSE: The aim of this study was to quantify changes in dimensions of nerves and muscle and the proportionate expression of neural antigens in infantile hypertrophic pyloric stenosis (IHPS). METHODS: Twenty specimens of pylorus from children with IHPS and age/sex-matched controls were examined using conventional histology and immunohistochemistry for a range of nerve and muscle antigens. The changes in the proportion of nerves expressing each antigen were quantified and statistically analyzed. RESULTS: The longitudinal muscle was found to be hypertrophic and protein gene product 9.5-stained nerves appeared longer and thicker in the myenteric plexus and shorter in the longitudinal muscle layer in IHPS. The proportion of nerves that expressed neural nitric oxide synthase (nNOS) was found to be diminished in all the IHPS tissues examined. In the circular muscle and myenteric plexus, the proportion of nerves that expressed vasoactive intestinal polypeptide (VIP) and nNOS was almost identically diminished. The expression of calcitonin gene-related polypeptide and substance P was proportionately reduced in the myenteric plexus. CONCLUSIONS: The results of this study represent the first quantitative analysis of nerves and muscle in IHPS. The muscle hypertrophy is not restricted to circular muscle layer. The changes in nerve morphology cannot be attributed to a dilutional effect of the muscle hypertrophy. The selective changes in nerve and ganglion morphology varies between tissue layers and neural antigen expressed. The findings of reduced proportions of nerves expressing, in particular, nNOS may shed some light on the etiology of this condition.