Liver transplant for metastatic pancreatoblastoma: 7-year event-free survival after chemotherapy, pancreatectomy, complete hepatectomy, and liver transplant.

Pancreatoblastoma is a rare malignant tumor in children. Surgical resection of the tumor is necessary for cure; however, due to its aggressive nature, it is often unresectable at presentation due to tumor size, local invasion, and/or metastasis. Because it is a rare tumor, there is currently no standard treatment regimen. We report a case of a 4-year-old boy who presented with metastatic pancreatoblastoma with multiple large metastases involving all four sectors of the liver. We began treatment with chemotherapy (cisplatin, 5FU, vincristine, and doxorubicin), which significantly reduced the tumor burden in both the pancreas and liver. We then performed a staged subtotal pancreatectomy, complete hepatectomy, and living donor left lateral segment liver transplant. This was followed by postoperative adjuvant chemotherapy. Our patient is alive and healthy and has now been tumor-free for 7 years with no tumor relapse.

Plasmapheresis treatment of antibody-mediated rejection in an A2 donor to O pediatric liver transplant recipient.

It is safe to transplant kidneys from blood group A2 donors into O recipients if the latter have low titers of anti-A antibodies. However, in liver transplantation, O and B recipients of A2 donor livers are not routinely screened for anti-blood group antibodies because of the immuno-absorptive capacity of the liver and the low incidence of antibody-mediated rejection. Herein, we report a rare case of combined cell and antibody-mediated rejection in a pediatric blood group O recipient of an A2 donor liver, and rescue of the allograft using PP and IVIG.

Vomiting and diarrhea.

Vomiting and diarrhea are frequently encountered in pediatric patients. Dehydration, a serious consequence of both vomiting and diarrhea, results in the deaths of more than 700 children annually in the United States. With appropriate parent education, both morbidity and mortality can be reduced, and much of the anxiety about these problems can be alleviated. Parents must be educated to recognize the associated signs and symptoms that indicate serious disease and warrant notifying the physician. Fluid therapy should be individualized, and parents should be informed of the appropriate steps to take. Parents must make quantitative observations and keep records not only to enable the physician to assess adequate fluid balance but also to be able to demonstrate to themselves the effectiveness of the treatment. It is just as important for the physician to reassure parents, who will have concerns about long-term nutritional or growth consequences.

Intra-arterial infusions and intestinal necrosis in the rabbit: potential hazards of umbilical artery injections of ampicillin, glucose, and sodium bicarbonate.

Umbilical artery catheters are frequently employed for administration of medications. When the catheter tip is positioned adjacent to major aortic tributaries or inadvertently in the mesenteric arteries, high concentrations of infused substances may perfuse the intestine. Injections of saline, 50% dextrose, 10% dextrose, 8.4% sodium bicarbonate, and 100 mg/ml ampicillin were made into a branch of the mesenteric artery supplying 10 to 15 cm of rabbit ileum. The intestine was then examined two to five days later. All segments of intestine perfused with saline and 10% dextrose were grossly and microscopically normal. In each of the eight sites perfused with 50% dextrose, intestinal necrosis was noted (P less than .001). Four of eight sites perfused with ampicillin had hemorrhage and villus atrophy (p less than .001). Of the eight sites perfused with sodium bicarbonate, three had necrosis with hemorrhage and five had villus edema. The data indicate that intraarterial infusions of high concentrations of sodium bicarbonate, glucose, and ampicillin produce serious lesions in an animal model. This suggests that appropriate precautions should be exercised when administering medications through the umbilical artery catheter.

Carbohydrate malabsorption in necrotizing enterocolitis.

A prospective investigation was conducted to determine if infants with necrotizing enterocolitis had evidence of carbohydrate intolerance prior to the onset of clinical symptoms of advanced disease. Stool specimens were examined for fecal reducing substances with Clintest tablets from well, full-term infants and sick premature infants. Only two of 45 (4.4%) formula-fed, full-term infants demonstrated higher than 2+ fecal reducing substances. Ten of 14 (71%) formula-fed premature infants who developed necrotizing enterocolitis had higher than 2+ reducing substances detected in their stools. Daily measurement of fecal reducing substances can be a useful adjunct in the management of sick premature infants.

Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study.

BACKGROUND: Celiac disease has a strong genetic association with HLA. However, this association only explains approximately half of the sibling risk for celiac disease. Therefore, other genes must be involved in susceptibility to celiac disease. We tested for linkage to genes or loci that could play a role in pathogenesis of celiac disease. METHODS: DNA samples, from members of 62 families with a minimum of two cases of celiac disease, were genotyped at HLA and at 13 candidate gene regions, including CD4, CTLA4, four T-cell receptor regions, and 7 insulin-dependent diabetes regions. Two-point and multipoint heterogeneity LOD (HLOD) scores were examined. RESULTS: The highest two-point and multipoint HLOD scores were obtained in the HLA region, with a two-point HLOD of 3.1 and a multipoint HLOD of 5.0. For the candidate genes, we found no evidence for linkage. CONCLUSIONS: Our significant evidence of linkage to HLA replicates the known linkage and association of HLA with CD. In our families, likely candidate genes did not explain the susceptibility to celiac disease.

Prevalence and clinical characteristics of celiac disease in Downs syndrome in a US study.

Celiac disease is an autoimmune gastrointestinal disorder characterized by mucosal atrophy of the jejunum on exposure to gluten, a protein found in grains. The purpose of our study was to determine the prevalence of celiac disease in children with Downs syndrome in a U.S.-based Caucasian population. The 97 Downs syndrome children were screened for celiac disease using serum IgA-anti-endomysial antibody testing, which is highly specific and sensitive for the disorder. Children with titers greater than 1:5 (using the IgA endomysial antibody [EMA] test; EMA+) were considered affected. Ten children (10.3%) were EMA+. We examined their HLA DQA1 DQB1 genotype, karyotype, clinical characteristics, and the prevalence of celiac disease in their first-degree relatives. The nine available karyotypes were trisomy 21. Downs syndrome-specific mean height percentile was 64%+/-26% (range <5-99%) and weight percentile was 43%+/-28% (range 5-95%). Presence of diarrhea, constipation, vomiting, and abdominal pain was similar for children with and without celiac disease. Only bloating symptoms were significantly more frequent in those with celiac disease (EMA+). Seven of eight (88%) genotyped EMA+ children had the celiac disease-associated high-risk HLA DQA1*0501 DQB1*0201 genotype as compared with 13/ 80 (16%) of EMA- children. Five of 48 (10%) first-degree relatives of the celiac disease (EMA+) children were EMA+. In conclusion, celiac disease, as diagnosed by positive endomysial antibody tests, has an increased prevalence in children with Downs syndrome in the U.S. as compared with the general population (1/250). Clinical and growth characteristics do not distinguish between children with and without celiac disease. Based on these observations, it is recommended that children with Downs syndrome be screened for celiac disease.

The utility of latex agglutination assays in the diagnosis of pediatric viral gastroenteritis.

To design a rapid and efficient protocol for processing pediatric stool specimens, the authors used 434 specimens to evaluate two commercial latex assays to detect rotavirus (Meritec-Rotavirus and Rotalex) and one to detect adenovirus (Adenolex). Rotavirus latex assay results were compared with electron microscopic examination and adenovirus latex assay results with virus culture. Ninety-two specimens (21%) were positive for rotavirus and 28 (6.5%) for adenovirus; 5 (1%) had both viruses. The sensitivity, specificity, positive predictive values, and negative predictive values for the three assays were, respectively, as follows: Meritec-Rotavirus (97%, 99%, 97%, 99%), Rotalex (91%, 99%, 94%, 98%), and Adenolex (46%, 99%, 77%, 97%). For primary rotavirus screening, the Meritec-Rotavirus and Rotalex latex assays offer a good alternative to electron microscopic examination. For primary adenovirus screening, the low sensitivity of the Adenolex latex assay precludes its use as a routine screen. Its excellent specificity, however, makes it a useful tool for culture confirmation.

Patterns of postcibal gastroesophageal reflux in symptomatic infants.

Symptomatic infants displayed three patterns of gastroesophageal reflux after drinking apple juice (20 ml/kg or 300 ml/m2 of body surface area). The type I pattern occurred in patients who had continuous postcibal gastroesophageal reflux, large hiatal hernias and frequently required an antireflux operation. A functional motility disorder suggesting delayed gastric emptying appeared to be important in infants with discontinuous reflux (type II pattern). These infants had frequent gastroesophageal reflux for only 2 3/4 hours postcibally, antral-pylorospasm, increased low esophageal sphincter pressures, and a high incidence of pulmonary symptoms and non-specific watery diarrhea. The mixed (type III) pattern of gastroesophageal reflux occurred in a small number of infants and exhibited features of both type I and II patterns.

Postcibal gastroesophageal reflux in children.

The effect of eating on childhood gastroesophageal reflux (GER) is unclear. Twenty-eight asymptomatic children and 28 children with symptoms of GER were fed apple juice or milk-formula and observed for 3 hr postcibal. Distal esophageal pH was monitored continuously during this interval and used to quantitate the frequency and duration of GER. A period of frequent GER occurred for up to 2 hr after apple juice feedings in asymptomatic children, whereas symptomatic patients had frequent GER for longer periods. Compared to apple juice feedings, milk-formula feedings resulted in a decreased esophageal acidity for the first 2 hr. However, the type of feeding did not affect GER seen in asymptomatic children more than 2 hr postcibal. The frequency and duration of postcibal GER were not reduced by the upright position in either group. Effective medical treatment of symptomatic children did not eliminate the frequent GER within 2 hr of apple juice feedings, whereas the Nissen fundoplication usually eliminated all GER. The absence of GER episodes following apple juice correlated with the inability of most children to burp or vomit following antireflux surgery. Therefore, frequent GER for up to 2 hr after clear liquid meals is probably physiologic in children. The effective control of vomiting by medical or surgical therapy correlated best with a decrease in GER more than 2 hr postcibal.

Genome-wide linkage analysis of 160 North American families with celiac disease.

Celiac disease (CD) is a common autoimmune disease caused by exposure to the protein gliadin in wheat, and related prolamins in barley and rye. The prevalence of the disease in the US is 1:133. The aim of this study was to identify non-human leukocyte antigen (HLA) loci that predispose to CD. A genome-wide search of 405 microsatellite markers was performed on DNA samples from 160 families with a minimum of two cases of CD. Multipoint, parametric and non-parametric linkage (NPL) analyses were performed. Locations on chromosomes 1q, 3q, 6p, 6q, 7q, 9q and 10q showed linkage statistics (NPL scores or heterogeneity logarithm of the odds (HLOD) scores) of approximately 2.0 or larger. The greatest evidence for linkage outside of chromosome 6 was on 7q and 9q. An NPL score of 2.60 occurred at position 151.0 on 7q and a HLOD score of 2.47 occurred at position 144.8 on 9q under a recessive model. As expected, there was highly significant linkage to the HLA region on 6p, with NPL and HLOD scores exceeding 5.50. In conclusion, this genome-wide linkage analysis represents one of the largest such studies of CD. The most promising region is a putative locus on 7q, a region reported independently in previous genome-wide searches.

Comparison of two rapid methods for detection of respiratory syncytial virus (RSV) (Testpack RSV and ortho RSV ELISA) with direct immunofluorescence and virus isolation for the diagnosis of pediatric RSV infection.

The ability of two commercial immunoassays to detect respiratory syncytial virus (RSV) in respiratory specimens was evaluated as follows: 152 specimens were tested by TestPack RSV (Abbott), and 72 were tested by Ortho RSV ELISA (Ortho). Test outcomes were compared with those of virus isolation alone, direct immunofluorescence assay (DFA) alone, or virus isolation and/or DFA. TestPack RSV versus virus isolation showed 91% sensitivity, 96% specificity, 93% positive predictive value (PPV), and 95% negative predictive value (NPV). TestPack RSV versus DFA showed 89% sensitivity, 97% specificity, 96% PPV, and 93% NPV. When TestPack RSV performance was compared with that of virus isolation and DFA, the sensitivity was 87% and the specificity was 100%. Ortho RSV ELISA versus virus isolation showed 88% sensitivity, 87% specificity, 79% PPV, and 93% NPV. Ortho RSV ELISA versus DFA showed 91% sensitivity, 88% specificity, 81% PPV and 95% NPV. When Ortho RSV ELISA performance was compared with that of virus isolation and DFA, the sensitivity was 86%, the specificity was 89%, the PPV was 86%, and the NPV was 89%. The accuracy of the TestPack RSV in combination with ease of performance and no need for specialized equipment or special skills make it an attractive alternative to DFA for rapid direct detection of RSV.

Serum alpha fetoprotein (AFP) levels in normal infants.

Serum alpha-fetoprotein (AFP) levels were monitored in 32 normal babies consecutively from 2 to 3 days, 2 wk, and 2 and 4 months after birth. In addition, serum AFP concentration was also measured in 116 random specimens from infants with normal liver enzymes and 10 infants born immaturely. Results were combined to establish normal AFP levels for infants at various ages. Serum AFP disappeared rapidly after birth. We found that it was not until 8 months of age that the normal AFP level in infants approached adult level. The half-lives of AFP degradation were estimated to be 5.5 days between birth and 2 wk, 11 days between 2 wk to 2 months, and 33 days between 2 and 4 months of age. In contrast to earlier belief, we felt that some AFP synthesis still exists after birth; however, the rate of synthesis may also decrease with age.

Sumatriptan in the treatment of cyclic vomiting.

OBJECTIVE: To describe a patient with cyclic vomiting who was treated successfully with sumatriptan, a serotonin, agonist. CASE SUMMARY: A patient with a 4-year history of cyclic vomiting was treated for an episode of nausea, vomiting, and abdominal pain. This patient had been hospitalized numerous times for cyclic vomiting over the previous 4 years, each hospitalization lasting from 3 to 11 days. Following a single subcutaneous injection of sumatriptan 6 mg, the patient ceased vomiting and was discharged 40 hours from the time of admission. DISCUSSION: The efficacy of sumatriptan in migraine headache appears to be mediated through its agonist activity at the serotonin1D receptor, resulting in constriction of dural blood vessels. According to published reports, therapeutic attempts at controlling cyclic vomiting often have included antimigraine therapies. Consistent with these reports, sumatriptan also appears effective in the treatment of cyclic vomiting. CONCLUSION: The pathogenesis of cyclic vomiting appears to share similarities with classic migraine, both of which may respond to sumatriptan therapy according to this report and previous work. Further study of the use of sumatriptan in the treatment of cyclic vomiting appears warranted.

Comparison of macronutrient concentration of preterm human milk between two milk expression techniques and two techniques for quantitation of energy.

Generally, when newborns in intensive care units receive human milk, we do not know the quantity of nutrients in that milk because such analysis is time-consuming and expensive. In our study, however, we sought to compare fat, protein, lactose, and energy concentration of a three-times-a-day sampling with a 24-h expression and to measure the difference between the calculated energy yield from protein, fat, and carbohydrate measurements and bomb calorimetry. At 14-18 days postpartum, 20 mothers of premature infants (30-34 weeks' gestation) expressed milk three times a day: 8 a.m., 12 p.m., and 8 p.m. At these three times, each mother expressed 3-5 ml of fore-milk and 3-5 ml of hind-milk for the sampling; the result was pooled for a 24-h expression. Only fat concentration differed significantly between fore- and hind-milk samples. Protein, fat, lactose, and energy concentration did not differ significantly between the two collection methods, 24-h expression and sampling. Moreover, we found no significant difference between the calculated number for energy content and the bomb calorimetry method of energy determination. The average fore- and hind-milk samples at 12 p.m. matched the 24-h milk expression. For clinical use, a milk sample obtained around 12 p.m. can predict macronutrient concentration, therefore allowing us to calculate an infant's approximate nutrient consumption.

Polarization coherent anti-Stokes Raman scattering microscopy.

We report polarization coherent anti-Stokes Raman scattering (P-CARS) microscopy that allows vibrational imaging with high sensitivity and spectral selectivity. The nonresonant background signals from both Raman scatterers and the solvent are efficiently suppressed in P-CARS microscopy. We demonstrate P-CARS imaging of unstained cells based on the contrast of the protein amide I band.

Gastroesophageal reflux causing respiratory distress and apnea in newborn infants.

Respiratory distress, apnea, and chronic pulmonary disease since birth were identified in 14 infants who also had symptomatic gastroesophageal reflux. Birth weights varied from 760 to 4,540 gm. All infants had radiographic changes similar to those in bronchopulmonary dysplasia. Cessation of apnea and improvement of pulmonary disease occurred only after medical (8) or surgical (6) control of gastroesophageal reflux. Simultaneous tracings of esophageal pH, heart rate, impedance pneumography, and nasal air flow in five infants demonstrated that reflux preceded apnea. Apnea could be induced by instillation of dilute acid, but not water or formula, into the esophagus. Prolonged monitoring of esophageal pH more than two hours after feeding in 14 other infants less than 6 weeks of age (birth weight 780 to 3,350 gm) without a history of recent vomiting indicated that reflux was not greater than in normal older children.

Hazards of calcium gluconate therapy in the newborn infant: intra-arterial injection producing intestinal necrosis in rabbit ileum.

Five infants received 10% calcium gluconate via umbilical artery catheters, which resulted in intestinal bleeding and lesions of the buttock, anus, groin, and thigh. The effects of intra-arterial calcium gluconate in two animal models were investigated. Injection of calcium into the aorta in the region of the posterior mesenteric artery resulted in immediate hyperperfusion of the descending colon; this may be an early hemodynamic response to injury in the area of colon supplied by this vessel. Injections into the arterial arcade of the rabbit ileum resulted in intestinal necrosis and villous atrophy. The use of umbilical artery catheters for administration of calcium gluconate is potentially hazardous.

Growth and plasma amino acid concentrations in term infants fed either whey-predominant formula or human milk.

We found no significant differences in mean growth measurements or mean plasma amino acid concentrations in 14 healthy full-term infants fed a whey-predominant cow milk formula and 15 healthy full-term infants who were breast-fed. Plasma taurine concentrations did not differ despite a tenfold higher level of taurine in human milk versus that in the formula. Plasma amino acid concentrations were measured one hour after feeding when the infants were 3 days and 2, 8, and 16 weeks of age. Weight, length, head circumference, crown-rump length, and skinfold thickness were measured at 3 days, 2 weeks, and 1, 2, 4, and 6 months of age. This study indicates that a whey-predominant cow milk formula compares favorably with human milk as a primary feeding for full-term infants.