Alan Daneman

Heterozygous mutations in the LDL Receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children

Three of 20 patients with juvenile osteoporosis were found to have a heterozygous mutation in the LRP5 gene. No mutations were found in the type I collagen genes. Mutations in the other family members with similar bone phenotype confirmed that LRP5 has a role in both juvenile and adult osteoporosis.

Intussusception. Part 3: Diagnosis and management of those with an identifiable or predisposing cause and those that reduce spontaneously.

In the previous two parts of this review on intussusception, the diagnosis and management of symptomatic, “idiopathic” ileocolic and ileoileocolic intussusceptions, which are considered to result from hyperplasia of lymphoid tissue in the distal ileum, were discussed. In this third part, those intussusceptions with an identifiable cause including pathologic lead point, those due to gastrojejunostomy or other feeding tubes, and those that are seen in the postoperative period as well as those that may be asymptomatic or may reduce spontaneously (usually limited to the small bowel) are discussed.

Correlation of sonographic findings and outcome in necrotizing enterocolitis

BackgroundThere is little in the literature regarding the use of gray-scale and Doppler sonography of the bowel in necrotizing enterocolitis (NEC) and how findings depicted by this modality might assist in predicting outcome and influence management.ObjectiveTo correlate sonographic findings with outcome in NEC.Materials and methodsThis was a retrospective analysis of clinical and abdominal ultrasonography (AUS) findings in NEC from January 2003 to December 2005. AUS findings were evaluated for portal venous gas, free gas, peritoneal fluid, bowel wall thickness, echogenicity, perfusion and intramural gas. Patients were categorized into two groups, according to their outcome.ResultsA total of 40 infants were identified who had AUS for NEC prior to any surgical intervention. Group A comprised 18 neonates treated medically and recovered fully, and group B comprised 22 neonates who required surgery or died. Free gas (six patients) and focal fluid collections (three patients) were only found in group B. Increased bowel wall echogenicity, absent bowel perfusion, portal venous gas, bowel wall thinning, bowel wall thickening, free fluid with echoes and intramural gas were seen in both groups, but more frequently in group B. Anechoic free fluid was seen more frequently in group A. Increased bowel perfusion was seen equally in both groups.ConclusionAn adverse outcome was associated with the sonographic findings of free gas, focal fluid collections or three or more of the following: increased bowel wall echogenicity, absent bowel perfusion, portal venous gas, bowel wall thinning, bowel wall thickening, free fluid with echoes and intramural gas. Sonographic findings are useful in predicting outcome and therefore might help guide management.

A Randomized, Controlled Trial of Heparin Versus Placebo Infusion to Prolong the Usability of Peripherally Placed Percutaneous Central Venous Catheters (PCVCs) in Neonates: The HIP (Heparin Infusion for PCVC) Study

BACKGROUND. Mechanical and infectious complications shorten the effective duration of peripherally inserted central venous catheters. Heparin use to prevent such complications and prolong the usability of peripherally inserted central venous catheters is inconclusive. OBJECTIVE. Our goal was to evaluate the effectiveness of heparin in prolonging the usability of peripherally inserted central venous catheters in neonates. DESIGN/METHODS. We performed a multicenter, randomized, controlled trial of heparin infusion (0.5 U/kg per hour) versus placebo for peripherally inserted central venous catheters in neonates. The primary outcome was duration of catheter use. Secondary outcomes were occlusion, catheter-related sepsis, thrombosis, and adverse effects of heparin. To detect a 168-hour (1-week) difference in the duration of catheter use, 192 patients were needed. Kaplan-Meier and Cox regression analyses were performed. RESULTS. A total of 201 neonates were enrolled (heparin group: n = 100; control group: n = 101). Baseline demographics were similar between the groups. Duration of catheter use was longer in the infants in the heparin versus the placebo group. Study center, gender, birth weight, and type and position of the catheter were not predictors of duration of catheter use. For those in the heparin versus the placebo group, the incidence of elective catheter removal (therapy completed) was 63% vs 42%, of occlusion was 6% vs 31%, of thrombosis was 20% vs 21%, and of catheter-related sepsis was 10% vs 6%, respectively. No adverse events were noted. CONCLUSIONS. Heparin infusion prolonged the duration of peripherally inserted central venous catheter usability, which permitted a higher percentage of neonates to complete therapy without increasing adverse effects.

Perforation during attempted intussusception reduction in children- a comparison of perforation with barium and air

This paper compares the effects on patients of perforation with barium and with air during attempted intussusception reduction by reviewing the clinical, radiological, surgical and pathological findings and sequelae in seven children who received barium and seven who received air. In both groups perforation occurred in infants under 6 months of age (with one exception) with a long duration of symptoms. All patients with barium enema required resection of bowel whereas only four with air enema required resection. Anesthetic times were longer in those patients with barium perforation in whom the intussusception did not move and there was a large leak. The patients with perforation due to air had a shorter hospital stay with decreased morbidity compared to those with perforation due to barium. Perforation occurred through areas of transmural necrosis in a minority of patients in each group. Perforations through normal bowel and shear injury (with air enema) indicate that increased pressure during the examination is an important factor in some patients. Because perforation with air is so much easier to deal with surgically and the children do better clinically, there is a tendency for some to consider perforation with air an inconsequential situation. However, a potential rare complication with this technique is tension pneumoperitoneum. Keeping this in mind, we continue to use air as the contrast of choice because the procedure in our hands is a safe, quicker and easier technique and we have achieved a substantial improvement in reduction rates. Overall reported perforation rates with air enema compare favourably with those due to barium enema.

Congenital mesoblastic nephroma: a clinicoradiologic study of 17 cases representing the pathologic spectrum of the disease.

Congenital mesoblastic nephroma (CMN) is a rare infantile renal tumor with a generally excellent prognosis. We describe 17 tumors that fit into the pathologic spectrum of CMN proposed by Beckwith, which ranges from benign renal tumors, through atypical “gray zone” lesions of more aggressive potential, to “crossover” tumors akin to clear cell sarcoma of kidney. Nine patients with histologically typical CMN were significantly younger and had smaller tumors than did eight patients with atypical CMN. Clinical features did not differ in the two groups of patients. A distinctive “ring sign” on renal sonography was commonly seen in patients with typical intrarenal CMN. All 17 patients were alive with no evidence of disease at a mean follow-up of 10 years. Nephrectomy was adequate therapy for younger infants and for those with typical CMN. Nephrectomy was probably also adequate therapy for infants 3 months of age or younger with atypical CMN, even if the tumor extended to the surgical resection margins and into the perinephric connective tissues. Adjuvant chemotherapy or radiation or both should be reserved for patients older than 3 months who have grossly unresected tumors and for those patients whose fumors have an unequivocally malignant histologic appearance or evidence of aggressive biologic behavior.

Imaging of the brain in full-term neonates: does sonography still play a role?

To date the literature comparing the usefulness of US and MR examinations of the neonatal brain suggests that US is not as effective a modality as MR. However, available studies were done on older equipment and published descriptions of the abnormalities found in the term brain are often incomplete. The purpose of this article is to emphasize technical factors that may be useful to optimize US imaging of the term neonatal brain, to provide a description of the sonographic findings in the brain in full-term neonates with hypoxic–ischaemic injury and to provide some data regarding the accuracy of sonography. While MR imaging may reveal abnormalities of the brain more floridly than sonography, we believe that sonography remains an extremely useful modality for evaluation of the full-term neonatal brain and it is probably a more accurate modality in this age group than the current literature suggests. Further prospective studies comparing sonographic and MR imaging findings are required to document the accuracy of sonography better and to help us define the role of this modality better. Such studies may help us select which patients really require MR imaging.

Risk factors, complications, and outcomes of gallstones in children: a single-center review.

Background and Objective: The increasing use of sonography has resulted in an increase in the proportion of children with gallstones who are asymptomatic at the time of diagnosis. In adults, the literature supports expectant management of clinically silent gallstones. The evidence for this management approach in children is limited to a number of small series. Our objective was to review the risk factors, complications, and outcomes of gallstones at our institution, particularly in those patients who are asymptomatic at the time of initial diagnosis. Materials and Methods: We reviewed 382 cases of gallstones in children. These patients were diagnosed with sonography. Data on age at diagnosis, presentation, sonographic findings, risk factors, complications, surgery, and follow-up were collected. A χ2 test was used to compare the complication rates between symptomatic and asymptomatic groups. Descriptive statistics were used to analyze the sample. Results: At diagnosis, 50.5% of children were asymptomatic; these patients were diagnosed at a mean age of 8.23 years. Compared with symptomatic patients, they were less likely to have a hemolytic anemia but more likely to have other risk factors, including cardiac surgery, leukemia and lymphoma, short bowel syndrome, or exposure to total parenteral nutrition or cephalosporins. These patients had a lower rate of complications than the symptomatic patients (4.6% vs 28.2% of symptomatic, P < 0.0001) and only 3.1% developed symptoms that necessitated surgery (vs 59.0% of symptomatic). Of the 58 (15.1%) diagnosed in infancy, 47 (81.0%) were asymptomatic. The infant group also had low rates of complications (8.6%) and cholecystectomy (1.7%). In cases with sonographic follow-up, resolution of gallstones was demonstrated in 16.5% of asymptomatic patients and in 34.1% of infants. Conclusions: The data suggest that clinically silent gallstones in children and infants are associated with low rates of complications and can be managed conservatively, unless complications occur. Patients with sickle cell disease, spherocytosis, and elliptocytosis had high complication rates and required surgery more often.

Unsuccessful air-enema reduction of intussusception: is a second attempt worthwhile?

Abstract Pneumatic reduction of idiopathic intussusception is successful in about 80% of cases, while 60% of the failures are reduced at surgery without resection. To determine whether delayed, repeated attempts at enema reduction of failures would reduce the need for operation in selected cases, over a 2-year period (1994–1996 inclusive), 17 infants with idiopathic intussusception underwent delayed repeat enemas 2–19 h following the first failed attempt at reduction. Clinical parameters and radiologic findings were evaluated with respect to outcome. Ten intussusceptions were successfully reduced after the second attempt in 9 and after the fourth attempt in 1. Seven children underwent a laparotomy, 5 because of failure of progressive reduction at air enema (AE). Two were taken to surgery early in the series, 1 because of perforation during a second attempt and 1 while awaiting a third reduction attempt. The 10 successful reductions all showed progressive movement of the intussusceptum on each AE; the 2 who perforated failed to show progressive reduction on their second AE. Because of these cases, the remaining 5 were referred to surgery because of failure of progressive reduction of the intussusceptum on the second attempt. At laparotomy, of the 7 unsuccessful reductions, 4 required resection and 3 had difficult manual reduction. The presence of vomiting, a mass, and/or bloody stools were not predictors of outcome. Failures had higher body temperatures (38.1 ± 0.3 vs 37.4 ± 0.1 °C, P = 0.07), heart rates (153.7 ± 8 vs 136.9 ± 2.1 min, P = 0.03), and longer duration of symptoms (36.8 ± 4 vs 21.3 ± 3.6 h; P = 0.01) than successes. Delayed repeat AEs may be safe and effective in selected cases of idiopathic intussusception, but should be considered only if significant movement of the intussusceptum is noted at each attempt. The ideal time for repeat AE reduction prior to surgery is not established, but 2–4 h appears appropriate. Pyrexia, tachycardia, and duration of symptoms greater than 36 h are relative contraindications to this course of management.

Congenital thymic cysts in children—Mostly misdiagnosed

BACKGROUND/PURPOSE Thymic cysts are rare lesions of the neck and mediastinum that are difficult to diagnose. Often considered inconsequential, these lesions can frequently be symptomatic. In this report the authors contrast their experience with that of the literature. METHODS From 1984 through 1997, the authors encountered 14 patients with this lesion. All cysts were completely excised. Patients that had an acquired cyst of the thymus were excluded from this series. RESULTS Of the 14 patients ranging in age from 2 weeks to 16 years, seven patients had cervical masses, five had mediastinal masses, and two children had both sites involved. Seven children were symptomatic with wheezing and upper respiratory infection, with cough and fever being the most common clinical features. Investigations included chest radiograph, contrast esophagram, sonography (US) and computerized tomography (CT). Displacement of vital mediastinal or neck structures was observed in eight patients. Only two patients received correct diagnosis before surgery. Successful and complete excision of all cysts was achieved. The cysts were benign and ranged in size from 2 to 22 cm in diameter. CONCLUSION Often forgotten, thymic cysts are rare benign lesions that should be considered in the differential diagnosis of cervical and mediastinal masses in children.