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.

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.

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.

Postpericardiotomy syndrome: no evidence for a viral etiology.

BACKGROUND: Postpericardiotomy syndrome has been considered a disorder induced by viral infection. This conclusion is based on serologic criterions, but these may be unreliable following either cardiopulmonary bypass or transfusion therapy. Previous studies have not verified the proposed etiology either by isolation of viruses, or by detection of their genome. We sought, therefore, to clarify the role, if any, of viruses in this syndrome. METHODS AND RESULTS: We studied prospectively 149 children aged from 6 months to 16 years who were undergoing open heart surgery. Blood samples were collected from all prior to operation, and again 7 to 10 days post-operatively, and 47 were sampled at the time of development of symptoms of pericardial involvement. Serums were analyzed for the presence of IgM and IgG antibodies to cytomegalovirus, herpes simplex virus, and Epstein-Barr virus. The polymerase chain reaction was used for amplification when assessing the genome of the enteroviruses. Cultures for viruses were established on samples of stool, urine, and throat swabs collected 7 days post-operatively, and at the time of postpericardial symptoms. Pericardial fluid obtained from 5 patients with the syndrome was cultured for viruses, and tested for enterovirus genome. On the basis of clinical and echocardiographic findings, 34 children were determined to have definite evidence of the syndrome, 13 were considered to have possible evidence, and the results from these patients were compared to those from patients with no pericardial symptoms, the latter being matched for age and transfusion status. We isolated viruses from one or more sites in five patients with definite evidence (16%), from one (9%) of those with possible evidence, and from seven (19%) of the controls. All serums and pericardial samples were negative for enterovirus genome. IgM antibodies were found in only 5 patients, three with symptoms of pericardial involvement and two without. Rates of seroconversion to IgG for the viruses were lower in the patients with symptoms of pericardial involvement compared to controls, but were strongly influenced by transfusion status. CONCLUSION: Our study has provided no evidence to support a viral etiology for the postpericardiotomy syndrome.

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.

Celiac disease and human leukocyte antigen genotype: accuracy of diagnosis in self-diagnosed individuals, dosage effect, and sibling risk.

BACKGROUND: Celiac disease is an autoimmune disorder of the small intestine characterized by intolerance to gluten. Traditionally, diagnosis is made by intestinal biopsy. Testing for immunoglobulin (Ig) A endomysial antibodies in the serum also is used for diagnosis. Biopsy and serology revert to normal with adherence to a gluten-free diet. Often, after an index case is diagnosed, siblings with symptoms adhere to a gluten-free diet without biopsy or serologic confirmation. More than 90% of patients with celiac disease have the human leukocyte antigen (HLA) DQA1*0501-DQB1*0201 genotype. Non-HLA genes also have been implicated. METHODS: One hundred ninety-five individuals with confirmed or suspected celiac disease were identified in 73 families affected by the disease. IgA endomysial antibody testing was performed for all symptomatic family members who did not have biopsy-confirmed diagnoses. DNA samples were genotyped at D6S276 and the HLA class II loci DQA and DQB. RESULTS: At the time sampling was begun in families, 88 of 177 (49.7%) individuals were self-diagnosed and adhering to a gluten-free diet. Ninety percent (91/101) of confirmed cases (biopsy or serology) had at least 1 copy of the DQA1*0501-DQB1*0201 genotype, whereas only 67% (46/69) of cases self-diagnosed (adherence to gluten-free diet without confirmation) had at least 1 copy. Of confirmed cases, 61% carried two copies of DQB*0201. It is estimated that the HLA association and other unlinked genes contribute approximately equally to the sibling risk of celiac disease. CONCLUSIONS: A dosage effect of DQB1*0201 may be associated with an increased risk of celiac disease. Self-diagnosis of celiac disease is as common as confirmed diagnosis in families in the United States. Diagnosis of celiac disease on the basis of clinical response to gluten restriction is inaccurate. With long-term adherence to a gluten-free diet, serologic test results are likely to be negative. Based on HLA genotype, approximately one third of self-diagnosed individuals are unlikely to have celiac disease. However, it is not possible to determine which individuals consuming a gluten-free diet have the disease. Therefore, before starting a gluten-free diet, serologic screening and biopsy confirmation are necessary.

Treatment of pediatric autoimmune enteropathy with tacrolimus (FK506).

Autoimmune enteropathy is characterized by chronic secretory diarrhea, villous atrophy, associated autoantibodies, and a partial response to immunosuppression. Currently available therapy (including steroids and cyclosporine) has resulted in remission only in a subset of patients. We evaluated the effects of tacrolimus (FK506) in patients with autoimmune enteropathy refractory to steroids and cyclosporine. Three patients with diagnosed autoimmune enteropathy who continued to have intractable diarrhea despite treatment with steroids and/or cyclosporine were treated with oral tacrolimus. Despite documented histological villous atrophy and poor absorption of oral cyclosporine, therapeutic tacrolimus levels were easily achieved in all 3 patients. All patients showed clinical improvement as documented by decreased stool output and ability to be weaned off parenteral nutrition; response time ranged from 1 to 4 months after tacrolimus was begun. Histological improvement was noted in all patients, and the small bowel biopsy specimens of 2 of the 3 patients showed a return to normal. All patients have been followed up for at least 6 months and are in clinical remission; 1 has received a bone marrow transplant for underlying immunodeficiency. Tacrolimus is a useful drug in the treatment of autoimmune enteropathy, even in patients who have not responded to steroids or cyclosporine. No long-term follow-up of patients with autoimmune enteropathy treated with tacrolimus is currently available.

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.

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.

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.

Effects of soy formulas on mineral metabolism in term infants.

We studied 40 healthy term infants who received a soy-based formula containing either a single carbohydrate (glucose polymers) or dual carbohydrates (glucose polymers and sucrose). Ten exclusively breast-fed infants served as controls for the first four months of the study. All infants were studied at 2 weeks, 2 months, and 4 months of age for anthropometric development, biochemical values, and bone mineral content. There were no differences among the three groups in weight, length, or head circumference gains. Serum levels of calcium, phosphorus, magnesium, copper, 25-hydroxycholecalciferol, and alkaline phosphatase were also similar. However, at 4 months of age, the breast-fed group had a higher plasma zinc level than both formula-fed groups, and at 2 and 4 months of age, it had higher bone mineral content and bone density.

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.

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.

Bone mineral status in childhood accidental fractures.

We studied the bone mineral and calcium (Ca) status of 17 children who suffered an accidental fracture in 1980. These children were matched by age and sex to a nonfractured control group. Blood was drawn for serum Ca, phosphorus, magnesium, 25-hydroxycholecalciferol ( calcidiol ), alkaline phosphatase, and albumin. Bone mineral content (BMC) was evaluated by photon absorptiometry. There were no differences in serum values between the two groups. Twelve (71%) of the 17 children in the fracture group had a lower BMC than their matched controls. The BMC of the fracture group was lower than their controls, 0.423 +/- 0.042 v 0.461 +/- 0.037 g/cm. Four of the 15 in the fracture group ingested less than 60% of the recommended dietary allowance (RDA) for Ca and P (800 mg/day), while all the controls were ingesting at least 60% of the RDA. Four children of the fracture group who were ingesting less Ca and P than those of the control group also had low BMC.

Lack of relationship of Clostridium difficile to antibiotic-associated diarrhea in children.

We studied prospectively the conversion rate to Clostridium difficile-positive stool cultures in 31 children receiving oral antibiotics for common infections and looked for a possible association of C. difficile colonization with diarrhea. The incidence of pretreatment positive stool cultures was 35% with the majority of positive findings in infants less than 1 year of age. After treatment with oral antibiotics C. difficile was cultured from the stool of 42% of the children. Eleven children developed diarrhea during antibiotic therapy. Seven of these children had at least one stool culture positive for C. difficile and four had persistently negative cultures. Oral antibiotic treatment of common infections in otherwise healthy children does not appear to predispose to stool colonization with C. difficile, nor is the presence of C. difficile in stools in these children significantly associated with the onset of antibiotic-associated diarrhea.

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.

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.