Duplicated or Hybridized Peptide Functional Domains Promote Oral Homeostasis.

Proteins that have existed for millions of years frequently contain repeats of functional domains within their primary structure, thereby improving their functional capacity. In the evolutionary young statherin protein contained within the in vivo-acquired enamel pellicle (AEP), we identified a single functional domain (DR9) located within the protein N-terminal portion that exhibits a higher affinity for hydroxyapatite and more efficient protection against enamel demineralization compared to other native statherin peptides. Thus, we tested the hypothesis that multiplication of functional domains of naturally occurring pellicle peptides amplifies protection against enamel demineralization. In addition, a specific amino acid sequence from histatin 3 (RR-14) was introduced to the hybrid peptides for further testing. Enamel specimens were sectioned to 150-µm thickness and randomly grouped as follows: DR9, DR9-DR9, DR9-RR14, statherin, histatin 1, or distilled water (control). After submersion for 2 h at 37°C, the specimens were placed in 2 mL demineralization solution for 12 d at 37°C. Upon sample removal, the remaining solution was subjected to colorimetric assays to determine the amount of calcium and phosphate released from each specimen. DR9-DR9 amplified protection against enamel demineralization when compared to single DR9 or statherin. Notably, the hybrid peptide DR9-RR14 demonstrated relatively strong protection when the antimicrobial property of these peptides was tested against Candida albicans and Streptococcus mutans. DR9-RR14 was able to maintain 50% of the antifungal activity compared with RR14 for C. albicans and similar values of S. mutans killing activity. This study has pioneered the functional exploration of the natural peptide constituents of the AEP and their evolution-inspired engineered peptides. The knowledge obtained here may provide a basis for the development of stable (proteinase-resistant) synthetic peptides for therapeutic use against dental caries, dental erosion, and/or oral candidiasis.

Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning.

We have recently shown that lymphocyte and monocyte recovery by day +100 are associated with survival post myeloablative allogeneic hematopoietic transplant for acute leukemia. We hypothesized that lymphocyte and monocyte recovery would have a similar impact on survival in the reduced intensity setting. To test this hypothesis, we analyzed clinical data from 118 consecutive fludarabine/melphalan-conditioned patients by correlating peripheral blood absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) at days +15, +30, +60 and +100 with the outcomes. Multivariate analysis revealed that day +100 AMC (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.07-0.73, P=0.01) and mild chronic GVHD (RR 0.09, 95% CI 0.005-0.43, P=0.008) were independently associated with survival. To explore whether the patterns of lymphocyte and monocyte recovery had a prognostic value, we performed unsupervised hierarchical clustering on the studied hematopoietic parameters and identified three patient clusters, A-C. Patient clusters A and B both had improved OS compared with cluster C (77.8 months vs not reached vs 22.3 months, respectively, P<0.001). No patient in cluster C had a day +100 AMC >300. Both severe acute GVHD and relapse occurred more frequently in cluster C. Our data suggest that patients with low AMC by day +100 post fludarabine/melphalan-conditioned allogeneic hematopoietic SCT may be at risk for poor outcomes.

Knee in early juvenile rheumatoid arthritis: MR imaging findings.

PURPOSE: To determine the magnetic resonance (MR) imaging findings in the knee in early juvenile rheumatoid arthritis. MATERIALS AND METHODS: MR imaging (1.5 T) was performed in the more symptomatic knee in 30 children with juvenile rheumatoid arthritis with a symptom duration 1 year or less. Conventional, fast spin-echo, three-dimensional gradient-echo, and gadolinium-enhanced T1-weighted images were assessed. Two radiologists independently read the images, and a third resolved disagreements. These images were compared with knee radiographs in 27 children. RESULTS: Mean maximal synovial thickness was 4.8 mm +/- 2.4 (SD). Mean synovial volume was 15.4 mL +/- 10.8. Suprapatellar joint effusions were seen in 26 (87%) of 30 knees, meniscal hypoplasia in 11 (37%) of 30 knees, and abnormal epiphyseal marrow in eight (27%) of 30 knees. Three knees had articular cartilage contour irregularity, fissures, and/or thinning. One knee had a bone erosion. Knee radiographs showed suprapatellar fullness in 78% of the knees, joint space narrowing in one knee, and no bone abnormalities. CONCLUSION: Synovial hypertrophy and joint effusions are the most frequent MR imaging findings of knees in early juvenile rheumatoid arthritis. Early in the disease, radiographically occult cartilage and bone erosions are uncommonly seen at MR imaging. The potential relationship of synovitis to cartilage abnormalities deserves further study.

Absent peritoneal fluid on screening trauma ultrasonography in children: a prospective comparison with computed tomography.

BACKGROUND: Although the accuracy of focused abdominal sonography for trauma (FAST) in adults has been demonstrated, results of this technique in children have been conflicting with few comparisons against computed tomography (CT), the imaging gold standard. METHODS: A total of 160 hemodynamically stable pediatric trauma victims referred for abdominal CT initially underwent rapid screening sonography looking for free fluid. Both studies were interpreted in blinded fashion. RESULTS: Forty-four of the 160 patients had an intraabdominal injury on CT, 24 (55%) of which had normal screening sonography. Fifteen of the 44 (34%) had no free fluid on either modality. Accuracy of sonography compared with CT was 76% with a negative predictive value 81%. CONCLUSIONS: Sonography for free fluid alone is not reliable to exclude blunt intraabdominal injury in hemodynamically stable children given the considerable percentage of injured patients without free fluid. J Pediatr Surg 36:565-569.

Pediatric peripherally inserted central catheters: complication rates related to catheter tip location.

OBJECTIVE: To compare complication rates between central venous catheter tip location and noncentral tip location after peripherally inserted central catheter (PICC) placement in children. METHODS: Between 1994 and 1998, data from all children who underwent PICC placement were analyzed. Patient demographics, catheter characteristics, catheter duration, infusate composition, and catheter complications were entered prospectively into a computerized database. Catheter tip locations were determined by fluoroscopy and were defined as central if they resided in the superior vena cava, right atrium, or high inferior vena cava at or above the level of the diaphragm, and as noncentral if located elsewhere. Differences in complication rates between the central and noncentral groups were analyzed. RESULTS: Data from a total of 1266 PICCs were analyzed from 1053 patients with a mean age of 6.49 +/-.2 years (range: 0-45.0 years). Of the 1266 PICCs, 1096 (87%) were central in tip location, and 170 (13%) were noncentral in tip location. The central group had 42 complications of 1096 catheters (3.8%), while the noncentral group had 49 complications of 170 catheters (28.8%). Controlling for patient age, catheter size, gender, and catheter duration with a logistic regression model, there remained a statistically significant increased likelihood of complication in the noncentral group versus the central group (adjusted odds ratio: 8.28; 95% confidence interval: 5.11-13.43). CONCLUSIONS: Centrally placed catheter tips are associated with fewer complications than are noncentrally placed catheter tips. Clinicians should ensure that catheter tips reside centrally after PICC placement in infants and children.

Demystifying the hospital information system/radiology information system integration process.

Most organizations planning to implement picture archiving and communications systems (PACS) are aware of the need to integrate the hospital information system (HIS) and radiology information system (RIS) with the PACS, yet few are acutely aware of the challenges associated with this requirement. This report highlights the results of collaborative efforts between Children's Hospital Medical Center-Cincinnati (CHMC) applications specialists with expertise in the HIS and CHMC information system, radiology staff familiar with the enterprise and radiology workflow and data flow requirements; and General Electric integration engineers familiar with the SMS HIS and RIS, and GE PACS. CHMC received Board approval, including full funding of the entire PACS project, in October 1998. An aggressive time frame for installation was established, as CHMC's PACS leadership committed to the selection, design, and implementation of PACS and computed radiography (CR) within 18 to 20 months. CHMC selected GE (Milwaukee, WI) as its PACS vendor in July 1999, and began its implementation in November 1999. We will present the four-stage integration process undertaken at CHMC: (1) planning the integration effort, (2) designing the Interface, (3) building the interface, and (4) testing the Interface.

Effect of surrogate tolerogenesis on the vascular rejection of pig heart xenografts.

BACKGROUND: Organ xenografts are fulminantly rejected by antibody-mediated vascular rejection. Surrogate tolerogenesis (ST), the induction of tolerance within the donor, is effective with aorta xenografts. This preliminary study assesses the effect of ST on preformed antibodies and rejection of porcine heart xenografts. METHODS: Tolerance to the donor pig was induced by infusing recipient marrow into fetal pigs. Later, pig splenocytes were transfused and heterotopic pig hearts transplanted using chimeric or nonchimeric pigs. Anti-pig antibodies were assessed. RESULTS: With ST alone, xenografts developed cellular rejection at 4-6 days, whereas control grafts developed vascular rejection at 3-4 days (cellular vs. vascular, P<0.03). There was a reduction in preformed antibodies (P<0.03). ST combined with moderate cyclosporine prevented rejection at 9+ and 25 days in sensitized recipients compared with vascular rejection at 0.5-2 days for controls (P<0.07). CONCLUSIONS: ST seems to provide protection against vascular rejection. The cellular rejection seems sensitive to cyclosporine.

Imaging and radiological interventional techniques for gastrointestinal bleeding in children.

Causes of pediatric gastrointestinal (GI) bleeding in children are numerous. The role of radiology in defining associated pathology, pinpointing the bleeding site, and intervening to control hemorrhage is discussed here. Barium studies, computed tomography (CT), and magnetic resonance imaging (MRI) each may play a role in identifying the underlying pathology associated with the bleeding. The exact source of bleeding may be localized by means of nuclear scintigraphy as well as selective angiography. In cases of life-threatening or persistent hemorrhage, once a bleeding source is identified, the interventional radiologist may offer percutaneous transcatheter therapy with selective intraarterial vasopressin infusion or embolotherapy.

Peripherally inserted central venous catheters: success of scalp-vein access in infants and newborns.

The authors assessed the feasibility of placing peripherally inserted central venous catheters via scalp veins in infants and newborns. In 60 newborns and infants, aged 3 days to 10 months, placement of 62 2-F peripherally inserted central venous catheters was attempted with scalpvein access. The tip location was central in 30 of the 62 catheters (48%) and long peripheral intravenous in 17 (27%); access failed in 15 (24%). Scalp-vein access for peripherally inserted central venous catheters offers a safe and effective alternative route for gaining central venous access in infants and newborns.

Tarsal coalition: a blinded comparison of MRI and CT.

OBJECTIVE: To determine how well MRI can detect tarsal coalition compared with CT, the current imaging standard. MATERIALS AND METHODS: Coronal and axial CT and MRI were performed within 3 weeks of each other on 40 feet in 20 consecutive patients referred with symptoms of possible tarsal coalition. Scans were read independently in blinded fashion by different imagers. Coalitions were either complete (osseous) or incomplete (non-osseous). Results were compared with available surgical data and clinical follow-up. RESULTS: Both modalities prospectively identified 15 coalitions (9 patients) and each missed 1 calcaneonavicular coalition. Twenty-three of the remaining 24 feet were negative for coalition on both CT and MRI. An atypical incomplete talocalcaneal coalition seen on CT was not identified prospectively on MRI. CONCLUSION: MRI is very good for detecting tarsal coalition and has a high rate of agreement with CT, the imaging "gold standard." When clinical suspicion for coalition is high, CT remains a more cost-effective diagnostic modality. If other causes for ankle pain are also entertained, MRI can be performed and provide nearly equivalent diagnostic accuracy for detecting tarsal coalition.

Fibrolipoma of the median nerve: MRI.

The MRI findings of two patients with fibrolipoma of median nerve are presented. A characteristic 'cable-like' appearance of the tumour was present on T1-weighted images. Unique imaging features of these cases included extension of the lesion into the radial digital nerve of the index finger in case 1 and extraneuronal extension of a exophytic fatty mass from the median nerve into the thenar eminence in case 2.

MR imaging of biliary cysts in children with biliary atresia: clinical associations and pathologic correlation.

OBJECTIVE: We used MR imaging to determine the prevalence of biliary cysts in children with end-stage biliary atresia and evaluated the association of cysts with cholangitis, choleretic therapy, portoenterostomy, biochemical abnormalities, and MR findings of end-stage liver disease. The MR features of these cysts were correlated with their gross and histopathologic appearances. MATERIALS AND METHODS: We retrospectively reviewed 48 MR studies, clinical history, and laboratory data of 44 consecutive children with biliary atresia. RESULTS: MR images showed cysts in eight patients (18%). Cysts were statistically (p < .04) more common in patients who had a history of cholangitis, but were not associated with choleretic therapy or portoenterostomy surgery. Cysts were not statistically correlated with abnormalities in hepatic biochemical function or MR features of end-stage liver disease. Four livers with cysts were available for histopathologic study. Cysts were filled with bile, and most had an epithelial lining, consistent with a biliary origin. The epithelium was frequently ulcerated, accompanied by periportal extravasation of bile and inflammation. These findings suggest chronic obstruction with microscopic perforation. CONCLUSION: Biliary cysts are common in biliary atresia and may be related to previous episodes of cholangitis with attendant obstruction of biliary radicles. The presence of these cysts did not correlate with hepatic function, portoenterostomy surgery, or the extent of liver disease.