Subset Of Pediatric Patients Research Articles

CT perfusion guided delayed recanalization with favorable outcome in pediatric stroke

There are no approved treatment options for acute ischemic stroke in the pediatric population. A case is presented of a 16-year-old boy with acute left-sided weakness who was transferred to...

Extragonadal Tumor and Testicular Microlithiasis: “Burned-out” Tumors Are Represented by Macrocalcification

To the Editor: The recent case report 1 and subsequent correspondence 2,3 raise some important issues surrounding the presence of testicular microlithiasis and nontesticular microlithiasis (macrocalcification) in both the pediatric and adult testis. We note the opinion of Harris 2 with regard to the occurrence of macrocalcification as more likely to represent the presence of a “burned-out” tumor rather than the presence of microlithiasis as advocated by Meyer and Gilbertson-Dahdal. 1,3 It seems to us unlikely that testicular microlithiasis is representative of a burned-out tumor as advocated by Meyer and Gilbertson-Dahdal. 1 Unfortunately the description and depiction of intratesticular calcification in many of the older articles they cite would not stand up to modern-day scrutiny; vague sonographic methods and assessment are only too evident (eg, Figure 4 in the article by Grantham et al 4 depicts areas of macrocalcification described as bright echogenic foci), likely a manifestation of the less sophisticated transducers of that period. The histologic characteristics of testicular microlithiasis are very different from those of the necrosis, macrocalcification, and possible tumor cell remnants associated with a burned-out tumor 5 ; testicular microlithiasis clearly shows calcified intratubular bodies on histologic specimens. 6 The sonographic features of testicular microlithiasis as classically described are unique to this entity and are not mimicked by other forms of intratesticular calcification. However, the underlying association of testicular microlithiasis as well as burned-out tumors (manifested by macrocalcification) with intratubular germ cell neoplasia, a precursor of a germ cell tumor, indicates an increased risk of tumor development in both testicular microlithiasis and macrocalcification groups. Hence, testicular microlithiasis is associated with intratubular germ cell neoplasia and with that association an increased risk of developing a tumor. Thus, an area of macrocalcification may represent a burned-out tumor, but the remainder of the testis remains at risk if intratubular germ cell neoplasia is present, and it usually is present. We believe that the finding of testicular microlithiasis in the case of Meyer and Gilbertson-Dahdal 1 is more likely to indicate the simultaneous presence of intratubular germ cell neoplasia and not areas of a burned-out tumor. The finding of testicular microlithiasis is incidental and is a marker of the risk associated with intratubular germ cell neoplasia, with no manifestation in the testis of a focal tumor or macrocalcification to indicate the origin in the testis of the retroperitoneal germ cell tumor: a truly “silent” testis for the presence of the source of the retroperitoneal germ cell tumor. Harris was unable to identify any studies that address the prevalence of macrocalcification. We have addressed the prevalence of all types of calcification on scrotal sonography and related it to the presence of primary testicular tumors in 3447 patients, 7 having earlier described in detail the types of scrotal calcification that may be encountered. 8 Any intratesticular calcification not typical of the description of microlithiasis was termed “nontesticular microlithiasis calcification (macrocalcification),” and this is the type of calcification that may be shown when a burnedout tumor is diagnosed in the presence of an extragonadal germ cell tumor, as indicated by the experience of Harris. 2 The prevalence of testicular microlithiasis in our study population was 2.0% (95% confidence interval [CI], 1.6%– 2.6%), and that of nontesticular microlithiasis calcification was 1.7% (95% CI, 1.3%–2.3%). The association with a metachronous primary germ cell tumor was significant in both types of intratesticular calcification. 7 A small subset of pediatric patients (n = 198) was also analyzed, with the prevalence of testicular microlithiasis recorded as 2.0% (95% CI, 0.6%–5.1%) and that of nontesticular microlithiasis recorded as 0.5% (95% CI, 0.0%–2.8%). Our figures, although not significant in the pediatric group with the small cohort analyzed, warrant further evaluation. A possible scenario would advocate that testicular microlithiasis is present in the pediatric population at the same level as that seen in the adult population, but nontesticular microlithiasis increases in the adult patient. This scenario would support the theory that nontesticular microlithiasis is a manifestation of a burned-out tumor that puts the patient at risk of developing a further germ cell tumor of the testis or is responsible for an existing extra gonadal germ cell tumor. There are scarce data to support this theory; it is time we looked more closely at the prevalence of testicular calcification in the pediatric population. We would agree with Harris 2 that a burned-out tumor is represented by nontesticular microlithiasis macrocalcification, and testicular microlithiasis has associations with germ cell tumors and extragonadal tumors. However, areas of testicular microlithiasis, as classically described on sonography, do not represent tumor involution.

9201 ORAL Complete Remissions Observed in a Subset of Pediatric Patients With CD30-expressing Malignant Lymphomas Treated in Clinical Studies of Brentuximab Vedotin (SGN-35)

M. Fanale, A. Franklin, R. Radhakrishnan, A. Termuhlen, A.K. Gopal, A. Shustov, D.A. Kennedy, E.L. Sievers. University of Texas MD Anderson Cancer Center, Department of Lymphoma and Myeloma, Houston TX, University of Texas MD Anderson Cancer Center, Department of Pediatrics Patient Care, Houston TX, Karmanos Cancer Institute, Hematology/Oncology, Detroit MI, Miller Children’s Hospital, Department of Pediatrics, Long Beach CA, University of Washington Medical Center, Medical Oncology Division, Seattle WA, University of Washington Medical Center, Hematology Division, Seattle WA, Seattle Genetics Inc, Clinical Affairs, Bothell WA, USA

Quality of Life Improves for Pediatric Patients After Total Pancreatectomy and Islet Autotransplant for Chronic Pancreatitis

Total pancreatectomy (TP) and islet autotransplant (IAT) have been used to treat patients with painful chronic pancreatitis. Initial studies indicated that most patients experienced significant pain relief, but there were few validated measures of quality of life. We investigated whether health-related quality of life improved among pediatric patients undergoing TP/IAT. Nineteen consecutive children (aged 5-18 years) undergoing TP/IAT from December 2006 to December 2009 at the University of Minnesota completed the Medical Outcomes Study 36-item Short Form (SF-36) health questionnaire before and after surgery. Insulin requirements were recorded. Before TP/IAT, patients had below average health-related quality of life, based on data from the Medical Outcomes Study SF-36; they had a mean physical component summary (PCS) score of 30 and mental component summary (MCS) score of 34 (2 and 1.5 standard deviations, respectively, below the mean for the US population). By 1 year after surgery, PCS and MCS scores improved to 50 and 46, respectively (global effect, PCS P < .001, MCS P = .06). Mean scores improved for all 8 component subscales. More than 60% of IAT recipients were insulin independent or required minimal insulin. Patients with prior surgical drainage procedures (Puestow) had lower yields of islets (P = .01) and greater incidence of insulin dependence (P = .04). Quality of life (physical and emotional components) significantly improve after TP/IAT in subsets of pediatric patients with severe chronic pancreatitis. Minimal or no insulin was required for most patients, although islet yield was reduced in patients with previous surgical drainage operations.

Targetoid spongiotic reaction pattern: A case series of seven paediatric patients

We present seven cases of a targetoid eruption, clinically mimicking erythema multiforme, occurring in paediatric patients aged 12 months to 14 years. All patients presented with a pruritic targetoid eruption on body and acral sites which spared mucosal areas. All patients demonstrated a spongiotic reaction pattern on histology without lichenoid change and demonstrated excellent responses to either oral prednisolone or topical corticosteroids. We propose the term 'targetoid spongiotic reaction pattern (TSRP)' for our subset of paediatric patients. We review the literature regarding targetoid eruptions in the paediatric population.

Treatment of children with recurrent high grade gliomas with a bevacizumab containing regimen

Children with recurrent high grade gliomas (HGG) have a dismal outcome with a median progression free survival (PFS) of 12 weeks. Adults with recurrent HGG treated with irinotecan and bevacizumab reportedly have a 63% response rate and a median PFS of 23 weeks. There is a paucity of corresponding published pediatric data. We retrospectively reviewed the records of patients less than 21 years of age with recurrent or progressive WHO grade 3-4 gliomas who were treated with bevacizumab containing regimens at our institution between January 2006 and September 2008. We identified eight patients. Six out of eight patients received irinotecan, temozolomide and bevacizumab, one patient received irinotecan and bevacizumab, and one patient received CCNU and bevacizumab. Three patients had stable disease for 30-93 weeks. The remaining five patients developed progressive disease within 17 weeks. The median PFS was 15 weeks and the 6-month PFS was 38%. Contrast enhancing disease responded or remained stable in five out of seven patients whereas non-enhancing disease progressed in three out of four patients. New distant non-enhancing lesions developed in three patients. The most common side effects included diarrhea, vomiting, thrombocytopenia and neutropenia. Bevacizumab was well tolerated when used in combination with conventional chemotherapy (irinotecan in most cases). PFS in our cohort was much shorter and the response rate was inferior in this small cohort of patients when compared with published adult data. However, bevacizumab containing regimens might be effective in a subset of pediatric patients, especially those with predominantly contrast-enhancing disease.

T cell response to viral antigens in adults and children with common variable immunodeficiency and specific antibody deficiency

Several T cell abnormalities have been described in common variable immunodeficiency (CVID), a B cell disorder of mainly unknown origin. A subset of CVID patients suffers from frequent reactivations of herpes viruses. We studied T cell function in CVID [and in a subset of paediatric patients with specific antibody deficiency (SAD)] by measuring T cell proliferation and cytokine production in response to herpes virus-antigens in paediatric CVID patients (n=9) and paediatric SAD patients (n=5), in adult CVID patients (n=14) and in healthy controls. Paediatric CVID patients, but not SAD patients, displayed moderately increased CD8+ T cell proliferation in response to cytomegalovirus, human herpes virus type 6B (HHV6-B) and herpes simplex virus compared to controls. CD8+ T cell responses in adult CVID patients tended to be increased in response to cytomegalovirus and herpes simplex virus. In response to stimulation with herpes virus antigens, the proinflammatory cytokines interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and interferon inducible protein (IP)-10 were produced. Overall, no major differences were detected in cytokine production upon stimulation between patients and controls, although higher IL-10 and IL-12 production was detected in paediatric patients. In conclusion, cellular immunity against herpes virus antigens appears undisturbed in CVID patients, although defects in subpopulations of CVID patients cannot be excluded.

Age-Dependent B Cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis

Multiple sclerosis (MS) typically manifests in early to mid adulthood, but there is increasing recognition of pediatric-onset MS, aided by improvements in imaging techniques. The immunological mechanisms of disease are largely unexplored in pediatric-onset MS, in part because studies have historically focused on adult-onset disease. We investigated autoantibodies to myelin surface Ags in a large cohort of pediatric MS cases by flow cytometric labeling of transfectants that expressed different myelin proteins. Although Abs to native myelin oligodendrocyte glycoprotein (MOG) were uncommon among adult-onset patients, a subset of pediatric patients had serum Abs that brightly labeled the MOG transfectant. Abs to two other myelin surface Ags were largely absent. Affinity purification of MOG Abs as well as competition of binding with soluble MOG documented their binding specificity. Such affinity purified Abs labeled myelin and glial cells in human CNS white matter as well as myelinated axons in gray matter. The prevalence of such autoantibodies was highest among patients with a very early onset of MS: 38.7% of patients less than 10 years of age at disease onset had MOG Abs, compared with 14.7% of patients in the 10- to 18-year age group. B cell autoimmunity to this myelin surface Ag is therefore most common in patients with a very early onset of MS.

Magnetoencephalography using total intravenous anesthesia in pediatric patients with intractable epilepsy: Lesional vs nonlesional epilepsy

Purpose: Magnetoencephalography (MEG) provides source localization of interictal spikes. We use total intravenous anesthesia (TIVA) with propofol to immobilize uncooperative children. We evaluate the effect of TIVA on interictal spikes in children who have intractable epilepsy with or without MRI lesions. Methods: We studied 28 children (3–14 years; mean, 6.6). We intravenously administered propofol (30–60 μg/kg/min) to record MEG with simultaneous EEG. We evaluated MEG spike sources (MEGSSs). We compared spikes on simultaneous EEG under TIVA with those on scalp video-EEG without TIVA. Results: There was a significant decrease in frequent spikes (10 patients, 36%) on simultaneous EEG under TIVA compared to those (22 patients, 79%) on scalp video-EEG without TIVA ( P < 0.01). MEGSSs were present in 21 (75%) of 28 patients. Clustered MEGSSs occurred in 15 (83%) of 18 lesional patients but in 3 (30%) of 10 nonlesional patients ( P < 0.05). MEGSSs were more frequently absent in nonlesional (6 patients, 60%) than lesional (one patient, 5%) patients ( P < 0.01). Thirteen patients with MRI and/or histopathologically confirmed neuronal migration disorder most frequently showed clustered MEGSSs (11 patients, 85%) compared to those of other lesional and nonlesional patients. Conclusion: Propofol-based TIVA reduced interictal spikes on simultaneous EEG. TIVA for MEG still had utility in identifying spike sources in a subset of pediatric patients with intractable epilepsy who were uncooperative and surgical candidates. In lesional patients, MEG under TIVA frequently localized the clustered MEGSSs. Neuronal migration disorders were intrinsically epileptogenic and produced clustered MEGSSs under TIVA. Nonlesional patients often had no MEGSS under TIVA.

Effect of submucosal alcohol injection on prolonged rectal prolapse in infants and children

Aim:Our aim in this study is to evaluate the effect of ethanol as a sclerosing agent on subset of pediatric patients with prolonged rectal prolapse.Materials and Methods:From 1997 to 2003, 165 cases of primary rectal prolapse were treated by submucosal injection of ethyl alcohol (96%) after 8 weeks of conservative therapy. Around 1.5-2 ml of alcohol was linearly injected in three sites (two laterals and one posterior).Results:Twelve of the 165 cases lost the follow-up and 153 cases were followed from 9 months to 6 years. One hundred and six patients (69.3%) had a duration of prolapse for 3-7 months. Forty patients (26.1%) had prolapse for more than 7 months and seven patients had prolapse for more than 1 year. One hundred and forty-seven out of 153 (96%) patients responded to single injection. Three of the children required a second injection. Three patients with age of more than 13 did not respond to the treatment. Twenty five cases had fecal soilage for few days. No infectious complication and no recurrence were observed.Conclusion:We concluded that 4-6 ml of ethyl alcohol (96%) is effective for the treatment of rectal prolapse. The duration of rectal prolapse had no deleterious effect on treatment; however, patients with age more than 13 years did not respond to sclerosing agent, probably due to different etiology.

Cytomegalic Interneurons

A defining histopathologic feature of Taylor-type cortical dysplasia (CD) is the presence of cytomegalic neurons and balloon cells. Most cytomegalic neurons appear to be pyramidal-shaped and glutamatergic. The present study demonstrates the presence of cytomegalic GABAergic interneurons in a subset of pediatric patients with severe CD. Cortical tissue samples from children with mild, severe, and non-CD pathologies were examined using morphologic and electrophysiologic techniques. By using in vitro slices, cytomegalic cells with characteristics consistent with interneurons were found in 6 of 10 patients with severe CD. Biocytin labeling demonstrated that cytomegalic interneurons had more dendrites than normal-appearing interneurons. Whole-cell patch clamp recordings showed that cytomegalic interneurons had increased membrane capacitance and time constant compared with normal-appearing interneurons. They also displayed signs of cellular hyperexcitability, evidenced by increased firing rates, decreased action potential inactivation, and the occurrence of spontaneous membrane depolarizations. Single-cell reverse transcription-polymerase chain reaction and immunohistochemistry for GABAergic markers provided further evidence that these cells were probably cytomegalic interneurons. The pathophysiologic significance of GABAergic cytomegalic interneurons in severe CD tissue is unknown, but they could inhibit glutamatergic cytomegalic pyramidal neurons, or contribute to the synchronization of neuronal networks and the propagation of ictal activity in a subset of pediatric patients with severe CD.

Do Pediatric and Adult Disaster Victims Differ? A Descriptive Analysis of Clinical Encounters from Four Natural Disaster DMAT Deployments

The differences between pediatric (< or = 17 years of age) and adult clinical field encounters were analyzed from four deployments of Disaster Medical Assistance Teams (DMATs). A retrospective cohort review of all patients who presented to DMAT field clinics during two hurricanes, one earthquake, and one flood was conducted. Descriptive statistics were used to analyze: (1) age; (2) gender; (3) severity category level; (4) chief complaint; (5) treatments provided; (6) discharge diagnosis; and (7) disposition. Five subsets of pediatric patients were analyzed further. Of the 2,196 patient encounters reviewed, 643 (29.5%) encounters were pediatric patients. Pediatric patients had a greater number of blank severity category levels than adults. Pediatric patients also were: (1) more likely to present with chief complaints of upper respiratory infections or wounds; (2) less likely to present with musculoskeletal pain or abdominal pain; and (3) equally likely to present with rashes. Pediatric patients were more likely to receive antibiotics, pain medication, and antihistamines, but were equally likely to need treatment for wounds. Dispositions to the hospital were less frequent for pediatric patients than for adults. Pediatric patients represent a substantial proportion of disaster victims at DMAT field clinics. They often necessitate special care requirements different from their adult counterparts. Pediatric-specific severity category criteria, treatment guidelines, equipment/medication stocks, and provider training are warranted for future DMAT response preparations.

Biofilm Surface Area in the Pediatric Nasopharynx

To compare the percentage of mucosal surface area of adenoids infected with biofilms removed from children with chronic rhinosinusitis (CRS) vs children with obstructive sleep apnea (OSA). Comparative microanatomical investigation of adenoid mucosa from patients with CRS and OSA using scanning electron microscopy. University-affiliated hospitals and ambulatory surgery center. Four girls and 12 boys ranging in age from 3 months to 10 years. Measurements of biofilm coverage of the entire adenoidal surface. Adenoids removed from patients with CRS had dense mature biofilms covering the mucosal surface; they had a mean of 94.9% of their mucosal surface covered with mature biofilms, compared with a mean of 1.9% coverage on the adenoids removed from patients with OSA. This difference was statistically significant at P < .001. Adenoids removed from patients with CRS had almost their entire mucosal surface covered with biofilms vs scant coverage for patients with OSA. Biofilms in the nasopharynx of children with CRS may act as a chronic reservoir for bacterial pathogens resistant to standard antibiotics. The mechanical debridement of the nasopharyngeal biofilms may explain the observed clinical benefit associated with adenoidectomy in this subset of pediatric patients.

Identification of adenoid biofilms in chronic rhinosinusitis

To compare the percent mucosal surface area of adenoids removed from children with chronic rhinosinusitis (CRS) and those with obstructive sleep apnea (OSA) infected with biofilms. Comparative micro-anatomic investigation of adenoid mucosa using scanning electron microscopy from patients with CRS and OSA. 4 females and 12 males ranging from 3 months to 10 years of age. Adenoids removed from patients with CRS had dense mature biofilms covering the mucosal surface. More specifically, adenoids removed from patients with CRS had an average of 94.9% of their mucosal surface covered with mature biofilms vs. an average of 1.9% coverage on the adenoids removed from patients with OSA. These differences were statistically significant at the p<0.001 level. It is well established that adenoidectomy is useful in the treatment of CRS resistant to antibiotics. Adenoids removed from patients with CRS had almost their entire mucosal surface covered with biofilms vs. scant coverage for patients with OSA (p<0.001). Decreased metabolic activity, decreased growth rate, and transmission of resistance genes all contribute to the antibiotic resistant nature of the biofilms. These metabolically sessile communities shed planktonic microorganisms on an intermittent basis. Therefore biofilms in the nasopharynx of children with CRS may act as a chronic reservoir for bacterial pathogens resistant to standard antibiotics. Also, the mechanical debridement of the nasopharyngeal biofilms may explain the observed clinical benefit associated with adenoidectomy in this subset of pediatric patients.

Risk of hearing impairment in pediatric liver transplant recipients: a single center study.

As survival rates following liver transplantation have increased, health care providers must assess the impact of transplantation on dimensions other than traditional medical measures. Hearing impairment may adversely impact social, emotional, cognitive, academic, and speech and language development. We hypothesized that children who undergo liver transplantation are at risk for hearing impairment due to exposure to ototoxic drugs. We conducted a review of 74 children who had undergone liver transplantation between December 1996 and September 2000 at Cincinnati Children's Hospital Medical Center. Hearing was assessed at discharge by an audiologist using age and developmentally appropriate techniques. The principal outcome measure was sensorineural hearing impairment. Independent variables were age at transplantation, United Network for Organ Sharing (UNOS) status at transplantation, primary diagnosis, post-transplant length of hospital stay, days of treatment with aminoglycosides, and days of treatment with loop diuretics. Eleven of 74 children (15%) had sensorineural hearing loss, of whom four had severe to profound hearing loss. Multivariate analyses showed that the adjusted relative risk for hearing loss in patients with hepatoblastoma was 66 and that there was a 5% increase risk for hearing loss for each additional day of hospitalization. Age at transplantation, UNOS status, and days of treatment with loop diuretics or aminoglycosides did not achieve significance in the model. Sensorineural hearing impairment occurs in a subset of pediatric patients following liver transplantation. Patients with hepatoblastoma or those who experience prolonged hospitalization after transplantation are at increased risk. Our observations are of particular importance for pediatric liver transplant recipients since the median age at transplantation is 12-18 months, a critical period for language acquisition.

Hepatic and hematological markers as predictors for the development of aplastic anemia in pediatric patients with indeterminate fulminant hepatic failure

AIMS: Apfastic anemia occm's intrequently in patients who undergo liver transplantation of indeterminate fulminant hepatic tadure (IFHF). This study evaluates the incidence of aplastic ane:ma and :be value of hepatic and hematological laboratory results that were obtained at the time o[ admission to a major pediatric liver transplant center [or fulminant hepatic failm~ (FHF), METHODS: All cases of pediatric FHF observed at UCLA since 1985 (n = 270) were retrospectively re~aewed. A group of liver transplant patients with indeterminate FHF and aplastie anemia (AA-FHF) (n = 8) was compared to group of patients with IFHF who received liver transplant and survived longer then 3 months (n = 37). Liver function and hematological markers such as albumin, ALT, ammonia, AST, bifirubin, fibrinogen, PT, WBC, hematocrit, hemoglobin and platelets were compared between the two groups. RESULTS: The lFHF group (n = 108) represented 40% of all patients who presented to UCLA with FHF. 65 out of 108 underwent liver transplantation and 83% survived. 20 of the 108 patients (18.5%) who sur~4ved were not transplanted. The AA-FHF groups represents 7.4% of the IFHF. The mean age in the /LR-FHF and control groups was 6.8 years and 6.1 years, respectively. Interestingly', all patients in the AA-FHF group were males, while the control group consisted of 52% males The admitting liver panels were compared between the two groups and there were no statistically s:gnificant differences seen. However, the AA-FHF subgroup had a significantly lower white blood cell count (WBC) (6.5 vs. 102, p = 0.024) and platelet count (123 vs. 195, p =0.042) on admission as compared to the control group. The AA~FHF group also had significantly fewer lymphocytes when compared to the control group, Moreover, the two groups appear to have a distinct pattern of the WBC and platelet counts when e~,afuated over the immediate post-transplant period, and were distinguishable within the first several post-operative days. CONCLUSIONS: Aplastic anemia is a significant complication that develops in a subset of pediatric patients who present with evidence of indeterminate FHF We have determined that patients with AA-FHF are more often to be males arm have early evidence of bone marrow dysfunction montks prior to developing clear clinical evidence of aplastie anemia. However, hepatic markers on admission were not tbnnd to correlate with the nsk of bone marrow dysfunction in this population,

Indolent course of advanced neuroblastoma in children older than 6 years at diagnosis.

An early observation suggests that children older than 6 years of age at diagnosis of neuroblastoma constitute a favorable prognostic group. Kaplan-Meier plots of survival of all such patients diagnosed at the Children's Hospital of Pittsburgh 1975-1992 were compared with curves of concurrently treated patients with Stage IV disease who were 1-6 years of age at diagnosis ("younger patients"). Known prognostic features, including stage and primary site of disease, pattern of metastases, histopathology, MYCN gene amplification, and urinary catecholamine metabolite ratios, were reviewed. Of 17 children diagnosed after the age of 6 years ("older patients"), 13 patients had Evans' Stage IV disease and 4 had Stage III disease. The median survival was 3.24 years (range, 0.63-15.04 years) for the entire cohort and 3.07 years for those children with Stage IV disease. This compared with a median survival of 1.05 years in 34 concurrent younger patients (P < 0.01). In most cases, disease in these older patients was characterized by a short-lived complete or partial remission followed by aggressive recurrent disease that was partially and only transiently chemo- or radiosensitive. Only 3 patients (2 with Stage IV disease) are in continuous complete remission at 3, 5 10/12, and 14 1/2 years from diagnosis. Although poor prognostic factors were common, including the presence of bony metastases (12/17), biopsy material from pretreatment tumor specimens demonstrated a single MYCN gene copy number in all patients and favorable histology in 15 of 16 samples. Older children with neuroblastoma have a more indolent course than do younger patients, a finding that appears to be related to favorable histology and the absence of MYCN amplification. Examination of larger numbers of such patients from cooperative groups should lead to a better understanding of what appears to be a subset of pediatric patients with neuroblastoma who may benefit from specifically tailored treatment protocols.

Single-Dose Pharmacokinetics of Cefpirome in Paediatric Patients???

The disposition of cefpirome was evaluated in 37 children and adolescents with normal renal and hepatic function who were between 1 and 18.8 years of age, after a single intravenous dose of 10 mg/kg (n = 14; 9.2 ± 5.6 years), 25 mg/kg (n = 13; 8.5 ± 6.3 years) or 50 mg/kg (n = 10; 10.1 ± 4.9 years). The drug was quantified from plasma and urine by high-performance liquid chromatography from repeated samples obtained over a 24-hour postdose period. Evaluable data suitable for pharmacokinetic analysis were available for 33 of the study participants (10, 13 and 10 participants in the 10, 25 and 50 mg/kg dose groups, respectively). Mean plasma concentrations at 0.25 and 8.0 hours postdose for the 10, 25 and 50 mg/kg dose groups were 35.6/1.4, 105.4/2.8 and 208.6/4.8 mg/L, respectively. The mean area under the plasma concentration vs time curve (AUC0–∞) estimated by the linear trapezoidal rule for the 10, 25 and 50 mg/kg dose groups was 51.1, 177.2 and 339.7 mg/L·h, respectively. Pharmacokinetic parameters for cefpirome were determined using NONMEM, which revealed that a triexponential function best described the disposition profile. Population pharmacokinetic parameters (mean ± SEM) using this model were as follows: t1/2α= 0.3 ± 0.05h, t1/2β = 1.4 ± 0.2h, t1/2γ= 6.5 ± 1.7h, plasma clearance (CL) = 2.7 ±0.1 ml/min/kg (180.0 ± 9.9 ml/min) and apparent steady-state volume of distribution (Vdss) = 0.6 ± 0.1 L/kg. The mean (± SD) renal clearance (CLR) and fraction of cefpirome excreted unchanged in the urine were 1.3 ± 0.8 ml/min/kg and 44.1 ± 22.3%, respectively. When data from a study of cefpirome pharmacokinetics in adults were included with the subset of paediatric patients studied, a significant, nonlinear inverse correlation was found between age and both Vdss and CL. Pharmacokinetic parameters for cefpirome would support the use of a 25 or 50 mg/kg dose given at a 12-hour interval for infants and children of more than 1 year of age.

The Anterior Cervical Approach for Traumatic Injuries to the Cervical Spine in Children

In most cases of traumatic cervical spine injuries in children, nonoperative treatment, mainly external stabilization, is sufficient. When operative treatment is chosen, surgeons often recommend posterior stabilization. In a subset of pediatric patients, the anterior approach is indicated. The anterior operative approach was employed in six children three to 14 years of age who sustained trauma to the cervical spine. The injuries included severe hyperflexion injury with crush fracture and avulsion of the vertebral body, fracture-dislocation of the vertebral body with involvement of the posterior elements and the disk, and injuries that caused major anatomic deformity of the cervical spine with cord compression. Anterior decompression with bony fusion led to normal anatomic alignment with neurologic improvement in all patients. Follow-up evaluation as long as eight years showed solid fusion and remodeling of the bone grafts. The anterior approach should be used more frequently as the surgical procedure of choice in children with traumatic lesions of the cervical spine. The anterior approach provided direct visualization of the lesion, which enabled effective repair and stabilization, early ambulation with minimal morbidity, and significant long-term neurologic improvement.

Unexpected Heterogeneity in E2A/PBX1 Fusion Messenger RNA Detected by the Polymerase Chain Reaction in Pediatric Patients With Acute Lymphoblastic Leukemia

Abstract The t(1;19)(q23;p13) is the most common recurring chromosomal translocation in childhood acute lymphoblastic leukemia (ALL) and has been associated with adverse prognosis. It involves the rearrangement of two genes, PBX1 and E2A, resulting in the production of transforming chimeric DNA-binding proteins. In all previous reports in which the presence of a chimeric transcript was described, the fusion point between the coding sequences of E2A and PBX1 was found to be constant at the RNA level. We have used RNA-based polymerase chain reaction (PCR) for the detection of E2A/PBX1 messenger RNAs (mRNAs) in children with ALL at the time of diagnosis. Of 21 patients exhibiting this rearrangement, 3 (14%) expressed a variant E2A/PBX1 transcript in addition to the expected one. The relative amounts of the two chimeric mRNAs varied between the patients, but remained constant in the same patient during different stages of the disease. Sequence analysis showed an identical insertion of 27 bp at the E2A/PBX1 junction of the variant RNA species, the translation of which would result in the replacement of Val478 by 10 amino acids. The inserted sequence has not been detected in any other human transcript besides the variant E2A/PBX1 RNA species and probably represents a splicing variant of the chimeric RNA. We conclude that a subset of pediatric patients with ALL that carry the E2A/PBX1 rearrangement express two types of the chimeric mRNA. The biologic significance of this additional E2A/PBX1 transcript is discussed.