Correction of odontoid dysplasia following bone-marrow transplantation and engraftment (in Hurler syndrome MPS 1H).

BACKGROUND: Odontoid dysplasia is recognized as a major component of the constellation of dysostosis multiplex lesions associated with Hurler's syndrome (MPS 1H). Because of this abnormality, there is an increased risk of atlantoaxial subluxation with potential cervical spinal cord injury. A significant alteration of the natural history of the disease with respect to the visceral, cardiac, and skeletal systems has resulted in an increased life span for MPS 1H patients associated with engraftment from normal donors. OBJECTIVE: The purpose of this study was to evaluate the longitudinal changes of odontoid dysplasia in MPS 1H following engraftment from bone-marrow transplantation (BMT). MATERIALS AND METHODS: A retrospective review of sequential plain film or cervical spine MR was performed in patients with MPS 1H. Odontoid morphology was graded as aplasia, severe dysplasia, moderate dysplasia, mild dysplasia, or normal. Odontoid morphology was plotted against the time interval. Fully engrafted, nontransplanted, and partially engrafted patients had careful imaging evaluation of the odontoid process. RESULTS: Ten patients were studied with a mean interval follow-up of 8.7 years post-BMT. Seven patients were totally engrafted. Two patients were nontransplanted, and one patient had only partial engraftment (20% enzyme activity). All totally engrafted patients had a progressive improvement in the grade of odontoid dysplasia following BMT. Patients with partial engraftment or without transplantation demonstrated static or increasing odontoid dysplasia. MR imaging showed abnormal dural soft-tissue masses at the level of C2 in all patients. Reduction in the grade of odontoid dysplasia was not associated with significant change in the appearance of the upper cervical soft-tissue masses. CONCLUSION: For the first time, this report documents that patients with MPS 1H show a decrease in the degree of odontoid dysplasia on imaging after successful engraftment following BMT.

Pulmonary cytolytic thrombi: a newly recognized complication of stem cell transplantation.

Over the past 5 years we have recognized a new pulmonary complication of hematopoietic stem cell transplantation (HSCT) associated with fever and pulmonary nodules termed 'pulmonary cytolytic thrombi' (PCT). Retrospective analysis of medical and radiographic records and pathologic material from 13 HSCT recipients with PCT and a review of the Blood and Marrow Transplant Database for all patients with radiographic evidence of pulmonary nodules or who underwent open-lung biopsy from 1 January 1993 to 31 December 1998 (n = 1228) were performed. The median age of patients with PCT was 11.9 years (range, 1.3-29.7 years). All patients developed fever at a median of 72 days (range, 8-343 days) post transplant, followed by pulmonary nodules on chest CT. Eleven patients were receiving therapy for active GVHD (acute, grades I-IV (n = 10); extensive chronic (n = 1)). Biopsy of the pulmonary nodules revealed a unique pattern of necrotic, basophilic thromboemboli with amorphous material suggestive of cellular breakdown products. This was descriptively labeled 'pulmonary cytolytic thrombi'. Immunohistochemical staining revealed entrapped leukocytes and disrupted endothelium, but was negative for histiocytes. Cultures and immunohistochemical stains were negative for infectious agents. Empiric therapy included systemic corticosteroids (n = 9) and amphotericin (n = 7). Nine patients survive with resolution of PCT at a median follow-up of 1.5 years. Bone Marrow Transplantation (2000) 25, 293-300.

Aortic dissection in young patients with chronic hypertension.

We describe four patients aged 14 to 21 years who developed acute aortic dissection. In three of the four patients, the course was fatal, despite aggressive medical and surgical intervention. All four patients had sustained systemic hypertension related to chronic renal insufficiency. The patients had no other identifiable risk factors for aortic dissection, including congenital cardiovascular disease, advanced atherosclerosis, vasculitis, trauma, pregnancy, or family history of aortic dissection. Although aortic dissection is rare in individuals younger than 40 years of age, young patients with sustained systemic hypertension are at increased risk for this serious and often fatal condition. Physicians must be aware of this rare complication of hypertension and consider aortic dissection in the differential diagnosis of unusual chest, abdominal, and back pain in hypertensive children, adolescents, and young adults.

Axillary artery aneurysm in tuberous sclerosis: cross-sectional imaging findings.

A 10-month-old boy with a known diagnosis of tuberous sclerosis presented with axillary and brachial masses. Cross-sectional imaging with computed tomography, magnetic resonance, and ultrasound demonstrated unsuspected aneurysms of the axillary and brachial arteries. The results of these studies significantly changed the preoperative planning for this patient, who was scheduled for a biopsy of a presumed soft-tissue tumor. To our knowledge, this is the first description of the cross-sectional imaging findings in the extremity peripheral vascular manifestation of tuberous sclerosis; it has only been previously described on angiography in one case. The rare association of peripheral arterial aneurysms with tuberous sclerosis is important to recognize not only for clinical diagnosis but also for appropriate surgical treatment and genetic counseling.

Syringomyelia in mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): imaging findings following bone marrow transplantation.

We present the imaging findings in a patient with mucopolysaccharidosis (MPS) type VI (Maroteaux-Lamy syndrome) who developed holocord syringomyelia. This represents the only reported case of syrinx formation in a child with MPS VI. Clinical, neurologic and spinal magnetic resonance imaging findings are presented. The patient has maintained a stable clinical and neurologic course over the period following allogeneic bone marrow transplant.

Magnetic resonance imaging of the pediatric airway.

OBJECTIVE: To determine the role of magnetic resonance imaging (MRI) and how it relates to endoscopy as well as to other imaging modalities in the evaluation of pediatric airway disorders. DESIGN: A review study of children with various distal airway disorders over a 3-year period. Surgical procedures as well as all diagnostic imaging modalities were reviewed and analyzed with respect to clinical outcome. SETTING: Academic tertiary care children's hospitals. PATIENTS: Forty-nine children between the ages of 1 week and 14 years with the signs and symptoms of distal airway disorders. INTERVENTIONS: Forty-five of 49 children underwent airway endoscopy. Fourteen children also underwent fluoroscopy and 4 underwent echocardiography. When indicated, open surgical repair was performed and used to verify findings in 32 cases. RESULTS: Magnetic resonance imaging was the most accurate modality in defining extrinsic airway abnormalities. The findings of echocardiography were incorrect in 2 of 4 cases, and fluoroscopy, although accurate for tracheal narrowing and tracheomalacia, often could not elucidate that exact cause or missed left mainstem bronchial compression. Furthermore, tracheal narrowing to 50% or greater on MRI correlated 100% with the need for surgical intervention. CONCLUSIONS: Magnetic resonance imaging is a useful modality that has allowed us to accurately diagnose extrinsic pediatric tracheal abnormalities. In certain cases, MRI scans can be obtained prior to endoscopy. In those cases, definitive endoscopy and open repair are performed at the same procedure instead of at 2 separate procedures (ie, one for diagnostic endoscopy and the other for definitive repair).

Microwave-accelerated direct immunofluorescent staining for respiratory syncytial virus and influenza A virus.

A microwave-accelerated direct immunofluorescence staining method which requires only 20 min from specimen receipt to interpretation is as effective as conventional methods for detecting respiratory syncytial virus and influenza A virus antigens in clinical specimens. The time required compares favorably with that for the less sensitive Abbott Test Pack RSV.

Adrenoleukodystrophy: a scoring method for brain MR observations.

PURPOSE: To develop a scoring method for brain observations in patients with X-linked adrenoleukodystrophy. METHODS: One hundred seventy-five brain MR scans in 83 male subjects less than 20 years of age with proved biochemical defects were reviewed. A severity score (0 to 34), based on a point system derived from location and extent of disease and the presence of focal and/or global atrophy, was calculated for each exam. RESULTS: Fifty-five of the 83 patients showed MR findings consistent with adrenoleukodystrophy. Two major patterns were observed. A posterior pattern (mean score, 9; range, 0.5 to 25) was present in 80% of patients, and an anterior pattern (mean score, 10; range, 2 to 18) was present in 15% of patients. Serial MR imaging, positive for adrenoleukodystrophy in 34 patients (mean follow-up, 23 months; range, 2 months to 6 years 11 months), showed progressive disease in 52%, progressive disease with subsequent stabilization in 18%, stable disease in 24%, and minimal improvement in 6%. CONCLUSION: The adrenoleukodystrophy MR severity scoring method is a measure that can be used with standard MR images. When used in conjunction with clinical parameters, this scoring method may help define better the natural history of adrenoleukodystrophy and monitor response to developing therapies.

Childhood cerebral form of adrenoleukodystrophy: short-term effect of bone marrow transplantation on brain MR observations.

PURPOSE: To report the serial brain MR observations in patients with childhood-onset cerebral adrenoleukodystrophy 1 to 2 years after bone marrow transplantation. METHODS: Eight boys with childhood-onset cerebral adrenoleukodystrophy have undergone successful transplantation at our institution. Seven patients (mean age, 8 years 10 months; range, 5 years 3 months to 11 years 9 months) had serial MR studies before and after transplantation. An MR severity score (0 to 34) based on disease location and the presence or absence of focal atrophy was calculated for each patient scan. RESULTS: Posttransplantation serial MR showed improvement in two patients, stabilization in three patients, and worsening of MR signal changes in two patients. The patient with the most striking progression had systemic graft-versus-host disease. Although the adrenoleukodystrophy MR severity score did not change in three patients after transplantation, two of these patients did show improved margination of disease. CONCLUSION: Bone marrow transplantation can affect brain MR observations in childhood-onset cerebral adrenoleukodystrophy. Although brain MR findings do not typically resolve, they do seem to stabilize, which is an improvement over the natural MR history of the disease.

Amyloid beta precursor protein and ubiquitin epitopes in human and experimental dystrophic axons. Ultrastructural localization.

Dystrophic axons (DA) represent a major pathological feature of several neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and Alzheimer disease. We have previously presented evidence that amyloid beta precursor protein (BPP) and ubiquitin (Ub) are present in DA of different origin. We have now characterized the immunoreactivity of DA experimentally induced in rat by the administration of parabromophenylacetylurea (BPAU) and examined the subcellular localization of Ub and BPP in BPAU-induced DA and in DA present in subjects affected by INAD. BPAU-induced DA strongly immunoreacted with antisera to Ub and to COOH- and NH2-terminal regions of BPP. Immunoblots of DA-enriched brain regions were consistent with an increase in the amount of Ub and BPP in DA. Moreover, BPAU-induced DA immunoreacted with antibodies to PGP 9.5, a neuronal-specific Ub COOH-terminal hydrolase, and to the inducible heat shock protein 70. Antigenic characterization also indicated that the tubulovesicular membranes within DA derived largely from the smooth endoplasmic reticulum rather than from the Golgi system or the synaptic vesicles. Subcellular immunolocalization of Ub and BPP in both INAD- and BPAU-induced DA revealed that Ub and BPP colocalize in granulovesicular material in both conditions. In INAD DA intense Ub immunoreactivity was also detected in nonmembranous electron dense structures that were present only in these DA, probably because of the chronic course of INAD. Although BPP immunostaining may be related to accumulation of BPP-containing membranes in DA, Ub immunostaining is likely to result from activation of the Ub system by the neuron in the attempt to remove excessive and possibly abnormal proteins. A similar pathogenesis can be postulated for DA of Alzheimer disease.

The effects of pore size and endothelial cell seeding upon the performance of small-diameter e-PTFE vascular grafts under controlled flow conditions.

The purpose of this study was to determine the effects of endothelial cell seeding and graft internodal distance upon the performance of 4-mm-ID e-PTFE grafts during acute reduced blood flow conditions. PTFE grafts especially manufactured with three different mean internodal distances (28, 40, and 52 microns) were evaluated. Fifteen dogs (n = 5 for each design of PTFE graft) underwent bilateral carotid artery replacements with 6 cm lengths of 4-mm-ID PTFE grafts. In each dog one graft was seeded with enzymatically derived endothelial cells; the contralateral graft was nonseeded. All grafts were evaluated 5 weeks postoperatively. Dogs with bilaterally patent grafts were subsequently subjected to flow conditions through the graft that were maintained at 30% of the initial flow rates for 4 hr. Following controlled low flows the grafts were excised and assessed for patency, thrombus-free surface area, inner capsule thickness and prostacyclin production. Endothelial cell seeding of these small-diameter e-PTFE vascular grafts improved patency and thrombus-free surface areas in grafts of all pore sizes, with these parameters being greatest in the 40-microns grafts. Inner-capsule healing in these grafts was controlled and related to the pore size. PGI2 production was improved in endothelial cell seeded grafts of all pore sizes. However, neither endothelial cell seeding nor graft pore size affected the performance of these e-PTFE grafts under conditions of reduced blood flows.

PCP abuse in New Orleans: a six-year study.

Methods for determination of PCP in body fluids are presented and a rapid screening method is suggested. The demographics, psychiatric profiles, forensic aspects, and diagnostic problems of PCP abuse are discussed.

Extended EMIT-DAU phencyclidine screen.

In a public hospital emergency room, 580 urines were screened for phencyclidine (PCP) with the routine EMIT-DAU PCP screen, the extended EMIT-DAU PCP screen, and a gas chromatograph/mass spectrometer/computer (GC/MS/COMP) in selected ion mode, which was chosen as the reference method. The extended method produced a 38.5% increase in positives detected over the routine EMIT-DAU PCP screen and allowed 66.4% of the specimens to be signed out as negative without confirmation by GC/MS/COMP. This ability to provide a rapid, relatively inexpensive screen for PCP in urine and, in particular, to eliminate those patients whose specimens are negative, is important in a psychiatric population that contains many acutely psychotic individuals with grossly abnormal behavior.

Arnold-Chiari malformation. Report of four cases with contamination of the central nervous system by amniotic contents.

Four patients with the Arnold-Chiari malformation had massive prenatal contamination of the spinal cord and brainstem (and also of the cerebral ventricles in one case) by amniotic squamous cells and lanugo hair, which had entered through open meningomyeloceles. Amniotic contents were present in the subarachnoid space, central canal, fourth ventricle, and aqueduct and were also embedded in neural tissue, causing severe gliosis, fibrosis, and blockage. The mechanism of the complication and its implications in the prognosis of patients with the Arnold-Chiari malformation are discussed.

4-Bromo-2,5-dimethoxyphenethylamine: identification of a new street drug.

The identification of 4-bromo-2,5-dimethoxyphenethylamine as a street drug is described. NMR, UV, and mass spectral data used in the identification of the compound are presented.

Phencyclidine abuse in New Orleans: medical, forensic, and laboratory aspects.

A one year study of phencyclidine abuse in New Orleans showed that 90% of the cases cannot be detected by routine laboratory methods. Fifty percent of all cases showed evidence of police intervention. Initial impressions covered a wide range of psychiatric and clinical diagnoses. Recurring psychiatric problems due to the presence of the drug would indicate observation for a period of at least 72 hours. Patterns of PCP abuse cross racial and ethnic boundaries and are found uniformly in all population groups.

Ethanol ingestion in children. A five-year review.

A five-year review at ethanol ingestions in children at Charity Hospital of Louisiana at New Orleans, revealed nine cases with blood ethanol levels in excess of 21.7 mmole/L (100 mg/dL); none resulted in death. We describe four patients in whom the blood ethanol levels were potentially life-threatening. In one case, we were able to follow the affected child's blood ethanol level serially; the rate of decrease was about twice that reported for an adult.