Biomedical subjects
Publications and source records attributed to L Spitz.
A boy with a long history of dysphagia attributed to neurological impairment was shown to have a large oesophageal foreign body. It had remained undetected for five years as a central lumen allowed the passage of liquids and semisolids. Foreign bodies must be excluded in children with dysphagia.
BACKGROUND: Improvements in the management of children with hepatoblastoma have followed advances made in cytotoxic agents and treatment regimens. The aim of this study was to quantify the effect of Lipiodol, an iodinated poppy-seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatoblastoma cells in culture. METHODS: Monolayer cultures of (1) a hepatoblastoma cell line generated from freshly explanted tumour tissue, (2) an immortal hepatoblastoma cell line (C3a) and (3) a human hepatocyte cell line were exposed to doxorubicin 10 microg/ml with or without 2 per cent Lipiodol for 1-72 h. The fluorescence intensity in the treated cells, which correlates with intracellular doxorubicin concentration, was measured by confocal laser scanning microscopy. Cytotoxicity was assessed by trypan blue exclusion and electron microscopy. RESULTS: Doxorubicin accumulated in the nucleus and cytoplasm of all the cell lines. With Lipiodol, the mean fluorescence intensity of intracellular doxorubicin was increased for up to 48 h in both hepatoblastoma lines, but not in the hepatocyte cell line. Lipiodol increased the uptake and intracellular concentration of doxorubicin in the hepatoblastoma cells in culture. Lipiodol also enhanced the cytotoxicity of doxorubicin on the cultured hepatoblastoma cells. CONCLUSION: Lipiodol significantly enhanced the uptake of doxorubicin by hepatoblastoma cells in culture. Lipiodol-doxorubicin targeted treatment of hepatoblastoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo, enabling a reduction in the total dose administered and side-effects.
BACKGROUND: Conjoined twins occur in approximately one in 200 000 live births. Their management is often extremely complex and experience with large numbers is restricted to a few centres worldwide. METHODS: An analysis of 17 sets of symmetrical conjoined twins managed by a single team of surgeons over a 16-year period was undertaken. RESULTS: Management could be divided into three groups. Those in group 1 (n = 5) had non-operative management, owing to cardiac fusion or gross anatomical union, and all died. Those in group 2 (n = 7) underwent emergency separation, when one twin was dead or threatening the survival of the sibling or where there was a correctable life-threatening associated anomaly (four of 14 survived). Twins in group 3 (n = 5) underwent elective separation, allowing time for detailed preoperative investigation and planning (eight of ten survived). CONCLUSION: Accurate preoperative investigation, a team approach, previous experience, and meticulous operative and postoperative management contributed to the success rate achieved in this series.
This study aimed to quantify the neural changes in congenital pyloric stenosis in dogs and to study the comparative anatomy between this condition in dogs and that in infantile hypertrophic pyloric stenosis. Eight specimens from the pylorus of dogs with pyloric stenosis and six control specimens were examined using conventional histology and immunohistochemistry for a range of neural antigens. The changes in the proportion of nerves immunoreactive for each antigen were quantified and analysed statistically. The morphology of the nerves in the diseased dogs was similar to that in controls. Only vasoactive intestinal peptide was reduced in expression in dogs (median proportion in control dogs 0.57, in diseased dogs 0.17; P = 0.065). This study demonstrates both morphological similarities and significant differences between closely related conditions in dogs, humans and other species.
OBJECTIVE: To describe the clinical features, treatment and outcome of functioning adrenocortical tumours in children, and to assess the value of tumour size as a marker for malignant potential. PATIENTS AND METHODS: Twenty-one children (mean age at presentation 4.9 years, range 0.6-11; 12 girls and nine boys) who presented with a functioning adrenal mass over a 29-year period (1972-2000) were assessed. Clinicopathological features and outcome information were obtained from a structured review of the case-notes. Before 1980 the diagnosis and staging was mainly obtained by intravenous pyelography and plain X-ray. Since 1980, ultrasonography, computed tomography and more recently magnetic resonance imaging were the methods of choice. RESULTS: The mean (range) duration of symptoms before diagnosis was 31 (2-108) months. The symptoms and signs at presentation comprised virilization (18 children), Cushingoid features (three), precocious puberty (three) and hypertension (four). Three children had malignant neoplasms, one presented with metastasis and of the other two, one died from the disease within 6 months, despite adjuvant chemotherapy and radiotherapy. The third girl is disease-free 11 years after complete excision of the neoplasm. Eighteen children had a benign neoplasm and all are alive and free of recurrence. In most of the children surgical extirpation was relatively simple, blood loss minimal, recovery uneventful and the hospital stay short (mean 5 days). The virilizing effects of all the neoplasms gradually resolved after surgery within a median (range) of 27 (6-108) months. CONCLUSIONS: Functioning adrenocortical neoplasms in children are rare, with a peak incidence in the first decade, are predominantly unilateral and more common in girls. Most are benign, but both benign and malignant lesions can present with virilizing and Cushingoid features. The malignant neoplasms have an extremely poor prognosis, especially if excision is incomplete, despite adjuvant chemotherapy and radiotherapy. Although there is an association between tumour size and malignancy, this cannot be used as a reliable individual discriminator.
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.
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AIMS: To compare the long term functional and psychosocial outcomes following surgical treatment for total colonic aganglionosis (TCA) with those in an age and gender matched group of patients with rectosigmoid aganglionosis (RSA). METHODS: Fifteen patients with TCA matched for age and gender with 15 patients with RSA were studied 7-17 years after the definitive operation. The internal and external sphincters were examined using anal endosonography. Functional outcome (faecal continence) was assessed by a surgeon not involved in the patients' care, and by a research psychologist in separate assessment sessions. The behavioural and emotional status of the patients was also assessed. RESULTS: Based on the surgeon's assessment, 6/15 TCA and 7/15 RSA patients were continent. In comparison, based on the psychological interview, 2/15 TCA and 6/15 RSA patients were continent. The TCA patients reported significantly more behavioural/emotional problems and lower levels of self esteem than the RSA patients. The parent and teacher assessments of psychosocial status revealed no differences between the groups. There was no association between incontinence and psychosocial adjustment in either group. There was no association between the assessments of functional outcome and the endosonographic appearance of the anal sphincters. CONCLUSIONS: The proportion of patients with faecal incontinence 7-17 years after definitive surgery was high in both groups, but no association was found between incontinence and the psychosocial outcome measures. TCA patients perceived themselves as less well adjusted than their matched pairs. Differences between the groups in length of hospitalisation and severity of illness, especially in infancy and early childhood, may account for these differences.
Lipiodol, a stable iodine addition product of fatty ethyl esters derived from poppyseed oil, has been used as a vehicle for targeted cytotoxic or radiotherapeutic treatment in adults with unresectable hepatocellular carcinoma and in a few children with advanced hepatoblastoma (HB). Prolonged retention of lipiodol by the cancer cells might enable more effective targeted therapy to advanced, multifocal, or metastatic HB. To investigate the uptake and cytotoxic efficacy of beta and Auger electron-emitting radioconjugates on HB cells, monolayers of HB (C3a, Hep Tow1) and normal human hepatocyte cell lines were exposed to lipiodol131 (L131), lipiodol125 (L125), or a cocktail of both isotopes. Uptake of radioactivity was assessed autoradiographically using phosphoimages and the cytotoxicity assessed by trypan blue exclusion and clonogenic assay. The uptake of the different radioconjugates was identical in both HB cell lines. The "cocktail" of both radioactive lipiodols caused the greatest cytotoxicity to HB C3a, and HepTow1. L125 alone had a similar level of uptake and cytotoxicity as L131. Radioactive iodine alone did not show any cytotoxicity on any of the liver cell lines in culture for up to 72 h. These experimental results provide support for a clinical strategy of combinations ("cocktails") of radioconjugates in targeted radiotherapy in patients with HB.
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Carnitine palmitoyltransferase I is assumed to be rate limiting for beta-oxidation in all tissues. However, the concentration of malonyl-CoA in heart and muscle is high and is enough to completely inhibit beta-oxidation if this assumption is correct. In this review, we consider whether: (i) there is a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity; (ii) the measured malonyl-CoA concentration in the heart is physiologically meaningful; and (iii) carnitine palmitoyltransferase I is rate-limiting for beta-oxidation in the heart.
BACKGROUND/PURPOSE: Intestinal ischaemia-reperfusion (IR) can cause liver failure. The aims of this work were to study the effects of intestinal IR on liver energy metabolism and to evaluate the effects of moderate hypothermia. METHODS: Intestinal IR (90-minute intestinal ischaemia plus 60-minute or 240-minute reperfusion) was achieved by clamping and unclamping the superior mesenteric artery in rats. Normothermia or moderate hypothermia (30 degrees to 33 degrees C) was maintained by adjusting the environmental temperature. The ratio of hepatic inorganic phosphate to adenosine triphosphate (ATP) was monitored continuously during intestinal IR using in vivo phosphorus ((31)P) magnetic resonance spectroscopy. Phosphorus metabolites also were measured in extracts prepared from freeze-clamped liver and intestine. RESULTS: Mortality occurred exclusively during normothermic intestinal IR. A progressive increase in the hepatic inorganic phosphate to ATP ratio after normothermic intestinal IR was observed. Moderate hypothermia delayed this effect. Analysis of liver extracts confirmed above findings. However, there was no difference in intestinal phosphocreatine or ATP between normothermic and hypothermic rats undergoing intestinal IR. CONCLUSIONS: Intestinal IR at normothermia was associated with liver energy failure and high mortality rate. Moderate hypothermia ameliorated liver energy failure but did not attenuate intestinal energy failure after intestinal IR. Hypothermia may prove to be useful in the management of patients with intestinal IR injuries in the future.
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.
BACKGROUND/PURPOSE: Lipopolysaccharide (LPS) and cytokines produced during neonatal sepsis trigger free radical production, which eventually results in inhibition of liver metabolism. Studies in adults have indicated a hypermetabolic response to sepsis; however, evidence for a hypermetabolic response in neonates is equivocal. This study was carried out to determine whether LPS and cytokines can cause liver hypermetabolism in neonates. METHODS: The initial bacterial insult and cytokine cascade were mimicked by the addition of lipopolysaccharide (Escherichia coli 055:B5), tumour necrosis factor (TNF-alpha), and interleukin-6 (IL6) during the isolation of hepatocytes by collagenase digestion from 11- to 13-day-old Wistar rats. Hepatocyte oxygen consumption was measured polarographically with cells respiring on palmitate (0.5 mmol/L). Myxothiazol, a specific inhibitor of mitochondrial respiration, was used to distinguish extra- and intramitochondrial oxygen consumption. Morphologic changes were assessed by electron microscopy. RESULTS: The addition of LPS, TNF-alpha and IL6 during hepatocyte isolation resulted in a 10% decrease in cell yield (P <.05) compared with untreated controls; however, cell viability was unchanged (n = 31). Both total and extramitochondrial oxygen consumption were significantly greater in treated cells compared with untreated controls (P <.05, Student's t test). Electron microscopy indicated that LPS, TNF-alpha, and IL6 did not cause ultrastructural changes to hepatocytes. CONCLUSIONS: The increase in oxygen consumption was predominantly extramitochondrial and likely to be caused by increased oxygen requirement for cytosolic detoxification and repair purposes. This study shows that liver hypermetabolism metabolism can occur in response to LPS and cytokines. However, during in vivo neonatal sepsis, additional free radical damage may blunt this hypermetabolic response.
PURPOSE: The aim of this study was to (1) characterize the source of additional medical information acquired by parents and (2) to verify how much information is correctly interpreted and remembered correctly. METHODS: A cross-sectional prospective study was made of parents of 108 children with surgical diseases consecutively admitted to a children's hospital in 1999. The median age of the children was 3 years (range, 0.01 to 16), and that of parents was 34 years (range, 18 to 54). Parental knowledge and understanding of their child's illness, operation, potential operative risk, and long-term outcome were scored on the basis of (1) parents' self appraisal (questionnaire) and (2) objective evaluation (interview) performed by one investigator not involved in the child's care. RESULTS: Parents' education included a university degree (15%), entry examination for university (13%), basic educational qualification (47%), and no educational qualification (15%). Additional medical information was obtained by 77% of the parents (63% from general practitioner, 46% from books, 31% from popular magazines, 24% from internet). Inadequate knowledge of illness and treatment was highlighted in 12% and 19% of the assessment made by interview, respectively, compared with 8% and 14% of the self appraisals. Inadequate knowledge of operative risk was higher in the assessment made by interview (42%) compared with self appraisal (9%; P <.0001). Similarly, inadequate knowledge of long-term outcome was higher in the interview (28%) compared with self appraisal (13%; P <.05). Acquisition of additional medical information irrespective of the source did not affect the accuracy of parental knowledge. Medical knowledge was more accurate in parents of children who required major operations and in those with higher educational qualifications (P <.05). CONCLUSIONS: Parents commonly obtain additional medical information. However, this information does not necessarily improve parents' understanding of the child's operative risk and long-term problems. Parents' perception of having adequate medical information often is incorrect.
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.
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.
PURPOSE: The aim of this study was to assess long-term educational attainment in adolescence of former infants who required major neonatal surgery. METHODS: The study is an extension of a prospective longitudinal study begun in 1983 on 30 full-term newborns requiring major neonatal surgery, a matched healthy control group, and full-term infants requiring neonatal intensive care for medical reasons. Educational attainment levels were obtained from the results of compulsory national curriculum examinations taken at age 11 years in 3 core academic subjects, English, Mathematics, and Science and teachers' assessments of current academic performance. Additionally, follow-up data on health were obtained from family general practitioners and parents. RESULTS: Seventy percent of the original surgical group, 48% of the original control group, and 77% of the original medical group underwent follow-up. The participants were aged between 11 and 13 years. After adjustment for social factors (gender, social group, and mother's age), the surgical group was significantly behind on all measures of educational attainment (English, P < .0005; Mathematics, P < .02; Science, P < .0005; academic performance, P = .004), compared with the control group and medical group who did not differ from each other. Independent predictors of outcome were mechanical ventilation for >or=4 days in the neonatal period and behavior problems at 3 years. At 12 months of age, independent predictors of cognitive functioning were length of hospitalization and, at 3 years of age, the number of operative procedures. Mechanical ventilation was not significantly associated with cognitive functioning at previous stages of the study. CONCLUSIONS: These results show that, in early adolescence, children who required major neonatal surgery were performing less well academically compared with their peers. This information can be used to increase awareness of the difficulties these children may experience during childhood so that intervention can be directed appropriately, thereby lessening the risk of later educational problems. J Pediatr Surg 36:858-862.