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M R DeBaun

Publications and source records attributed to M R DeBaun.

35 records · Page 2Linked to original sources
PubMed1998

Sickle cell disease: imaging of cerebrovascular complications.

This case is reported because of the unusual blood findings, no duplicate of which I have ever seen described. Whether the blood picture represents merely a freakish poikilocytosis or is dependent on some peculiar physical or chemical condition of the blood, or is characteristic of some particular disease, I cannot at present answer. I report some details that may seem non-essential, thinking that if a similar blood condition is found in some other case a comparison of clinical conditions may help in solving the problem.

Adolescent↗
PubMed1998

Cognitive screening examinations for silent cerebral infarcts in sickle cell disease.

OBJECTIVE: In children with sickle cell disease (SCD), silent cerebral infarcts are the most frequent cause of neurologic injury. We determined the sensitivity and specificity of selective neurocognitive measures when separating children with silent cerebral infarcts and SCD from sibling controls. Additionally, we tested the validity of the same cognitive measures to identify patients with overt strokes. METHODS: We examined performance on a neuropsychologic battery containing measures of attention/executive, spatial, language, memory, and motor functioning for seven children with SCD and silent cerebral infarct, 21 children with SCD and overt stroke, and 17 normal siblings. Diagnosis of cerebral infarct was based on results of MRI. RESULTS: Measures from the attention and executive domains were the most useful for identifying children with silent cerebral infarct. The Test of Variables of Attention was the most robust measure and yielded a sensitivity rate of 86% and a specificity rate of 81%. This measure also showed a sensitivity rate of 95% in identifying overt stroke. CONCLUSIONS: Brief cognitive screening measures, if properly constructed, may be an effective means of identifying children with silent cerebral infarct. Future prospective studies should be pursued to assess the utility of cognitive screening for silent cerebral infarcts in SCD.

Adolescent↗
PubMed1998

Chest radiography as a predictor of outcome in posttransplantation lymphoproliferative disorder in lung allograft recipients.

OBJECTIVE: The radiologic findings of posttransplantation lymphoproliferative disorder in lung transplant recipients have received little attention compared with the findings for recipients of other solid organ transplants. We describe the intrathoracic findings and explore whether the radiographic presentation can predict outcome. MATERIALS AND METHODS: Twenty-six patients (mean age, 32 years; range, 2-63 years; 18 female, eight male) with histologically proven lymphoproliferative disorder were identified from 518 lung transplantation patients, a 5.0% frequency. Chest radiographs, obtained within 1 week of diagnosis, were compared with baseline posttransplantation radiographs for all 26 patients and with chest CT scans for 20 patients. RESULTS: The interval between transplantation and diagnosis ranged from 6 weeks to 7 years (mean, 16 months; median, 6 months). The thorax was involved in 18 (69%) of 26 patients. A new chest radiographic abnormality was present in all 18 patients and provided the first indication of disease in 14 (78%) of 18 patients. The most common finding was a solitary pulmonary nodule, seen in nine (50%) of 18 patients. Other findings included multiple nodules, multifocal alveolar infiltrates, and hilar and mediastinal adenopathy. CT scans detected additional nodules and lymph nodes but did not show occult disease in any case that appeared normal on radiography. Eight (89%) of nine patients with solitary pulmonary nodules at presentation were alive 1 year after diagnosis, compared with six (35%) of 17 patients with other presentations (p < .01). CONCLUSION: Thoracic manifestations are present in most lung transplant recipients with lymphoproliferative disorder. Patients with solitary nodules have a better outcome in the first year after diagnosis than do patients with other presentations.

Adolescent↗
PubMed1998

Nonmalignant renal disease in pediatric patients with Beckwith-Wiedemann syndrome.

OBJECTIVE: The objective of this retrospective review was to determine the incidence and spectrum of nonmalignant renal disease in patients with Beckwith-Wiedemann syndrome. MATERIALS AND METHODS: Patient records were obtained from the Beckwith-Wiedemann Registry of the National Cancer Institute. Imaging findings and medical records of 152 neonates, infants, children, and adults with Beckwith-Wiedemann syndrome (age range, 1 day to 30 years old; median age, 1 year 3 months old) were retrospectively reviewed by three radiologists. Available pathologic material also was reviewed. RESULTS: Thirty-eight (25%) of 152 patients with Beckwith-Wiedemann syndrome had 45 nonmalignant renal abnormalities, including medullary renal cysts (n = 19, 13%), caliceal diverticula (n = 2, 1%), hydronephrosis (n = 18, 12%), and nephrolithiasis (n = 6, 4%). Thirty-three (87%) of the 38 patients with nonmalignant renal disease were asymptomatic. Clinical manifestations of the remaining five patients included urinary tract infections (n = 4) and flank pain due to obstructive stone disease (n = 1). Nonmalignant renal disease was mistaken for Wilms' tumor in two patients, resulting in unnecessary nephrectomies. Seven children (18%) had Wilms' tumor and nonmalignant renal disease. CONCLUSION: Nonmalignant renal abnormalities occur in approximately 25% of patients with Beckwith-Wiedemann syndrome but are generally asymptomatic. Nonmalignant renal abnormalities should be considered in the differential diagnosis of a mass revealed during screening sonography of a patient with Beckwith-Wiedemann syndrome to avoid unnecessary surgery.

Adolescent↗
PubMed1996

Reduced expression of the cyclin-dependent kinase inhibitor gene p57KIP2 in Wilms' tumor.

We have previously shown that the p57KIP2 gene, which encodes a cyclin-dependent kinase inhibitor, undergoes genomic imprinting and lies within a 700-kb domain of imprinted genes on 11p15, including IGF2 and H19. Loss of heterozygosity and loss of imprinting (LOI) of this region are frequently observed in Wilms' tumor (WT) and other embryonal malignancies. Although LOI of p57KIP2 was observed in some WTs (approximately 10%), allele-specific expression was preserved in most tumors examined. Because our initial studies were inconclusive concerning the absolute expression level of p57KIP2 in WT, we developed a sensitive and quantitative RNase protection assay to determine if changes in p57KIP2 expression play a role in WT. Expression of p57KIP2 was found to be virtually absent in 21 of 21 WTs compared to matched normal kidney from the same patients, as well as compared to fetal kidney. We also examined p57KIP2 expression in the normal kidney and tongue of patients with Beckwith-Wiedemann syndrome (BWS), which predisposes to WT and also involves LOI of IGF2 and H19. Although p57KIP2 was undetectable in BWS tongue, similar results were also observed in postnatal non-BWS tongue samples. Most primary skin fibroblast cultures of BWS cell lines exhibited normal imprinting of p57KIP2. However, one BWS patient did show LOI of p57KIP2 in skin fibroblasts. Thus, p57KIP2 is part of a domain of genes on 11p15 that show altered expression and, in some cases, altered imprinting in WT and BWS.

Beckwith-Wiedemann Syndrome↗
PubMed1996

Screening for Wilms' tumor in children with high-risk congenital syndromes: considerations for an intervention trial.

Screening for cancer in children is uncommon. However, in children with congenital syndromes associated with Wilms' tumor, conditions exist that potentially make screening effective. This select population of children 1) are relatively easily identified; 2) have a high incidence of Wilms' tumor; 3) if identified before development of Wilms' tumor, may have a decrement in morbidity/mortality; and 4) are amenable to a simple and acceptable screening technology, renal sonography exams. Many clinicians have recommended screening for cancer in children with congenital syndromes associated with Wilms' tumor. However, neither costs nor effectiveness of such recommendations have been evaluated systematically. The strongest evidence for or against Wilms' tumor screening in this select population would be provided by a randomized screening trial. Prior to undertaking such a trial, the key parameters that dominate the cost and effectiveness of screening should be identified. Simulation models, such as cost effectiveness analysis, offer a starting point for deciding whether cancer screening is appropriate, and if so, under what set of conditions. We review basic conditions required for a successful screening trial in children with syndromes that are at increased risk of Wilms' tumor. We also discuss the use of cost-effectiveness analysis as a preliminary step in determining the feasibility of an intervention trial.

Child↗
PubMed1996

Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia: effects of continued penicillin prophylaxis.

OBJECTIVES: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years in children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses. STUDY DESIGN: Children with sickle cell anemia, who had been treated with prophylactic penicillin for at least 2 years before their fifth birthday, were randomly selected at age 5 years to continue penicillin prophylaxis or to receive placebo treatment. These children had been immunized once or twice in early childhood with pneumococcal polysaccharide vaccine and were reimmunized at the time of randomization. RESULTS: Serotype-specific IgG antibody responses to reimmunization varied according to pneumococcal serotype but in general were mediocre or poor; the poorest response was to serotype 6B. The antibody responses were similar in subjects with continued penicillin prophylaxis or placebo treatment, and in subjects who received one or two pneumococcal vaccinations before reimmunization. The occurrence of pneumococcal bacteremia was associated with low IgG antibody concentrations to the infecting serotype. CONCLUSIONS: Reimmunization of children with sickle cell anemia who received pneumococcal polysaccharide vaccine at age 5 years induces limited production of serotype-specific IgG antibodies, regardless of previous pneumococcal vaccine history. Continued penicillin prophylaxis does not interfere with serotype-specific IgG antibody responses to reimmunization.

Adult↗
PubMed1995

Lung cancer and CYP2D6 (the debrisoquine polymorphism): sources of heterogeneity in the proposed association.

Lung cancer association studies have yielded suggestive but not definitive results for a few genes: CYP1A1 (in Japanese), GSTM1 and CYP2D6. We focus on variability in studies of lung cancer and the CYP2D6 gene (debrisoquine metabolic phenotype) as an instructive case and we propose some sources for this heterogeneity. Beyond the general sources of bias in all field studies, three specific concerns are relevant. First, evidence that CYP2D6 is expressed in the brain. The metabolic phenotypes have distinct psychological profiles and therefore there is the potential to distort studies through selection bias. Second, among the lung cancer histologic types, adenocarcinoma likely does not share increased genetic susceptibility due to CYP2D6. Third, the degree of smoking is likely to be related to genetic susceptibility. Effect modification by smoking should be sought for any putative genetic marker for lung cancer. Progress in understanding genetic susceptibility is likely to depend on future well-designed studies that adjust for these and other sources of bias. We are currently reanalyzing the original data from the published studies in order to further explore these issues.

Aged↗
PubMed1995

Noninvasive central nervous system imaging in sickle cell anemia. A preliminary study comparing transcranial Doppler with magnetic resonance angiography.

PURPOSE: We evaluated the accuracy of transcranial Doppler (TCD) and magnetic resonance angiography (MRA) as a screening modality for cerebral infarct in patients with sickle cell disease. PATIENTS AND METHODS: Twenty-four patients with sickle cell disease were assessed for a cerebral infarct. Each patient underwent neurologic examination, psychometric evaluation, magnetic resonance imaging (MRI), MRA, and TCD. Presence of a cerebral infarct was determined by an MRI and supported by neurologic and neuropsychometric evaluation. All investigators were unaware of the patient's status. Cerebral vasculature by MRA was categorized as being occluded, stenotic, or normal. The maximum TCD velocity of the right and left middle cerebral artery were assessed. Various cutoffs were used to determine the sensitivity and specificity of TCD. RESULTS: MRA had a sensitivity and specificity of 100% and 92%, respectively. At a maximum velocity cutoff of 180 cm/s, the sensitivity and specificity of TCD were 20% and 67%, respectively. No maximum velocity on TCD produced both sensitivity and specificity > 50%. CONCLUSION: MRA is more sensitive than TCD when the middle cerebral artery for maximum velocity is compared. Prospective evaluation is warranted to determine if TCD is useful as a screening technique for cerebral infarction in children with SCD.

Anemia, Sickle Cell↗
PubMed1995

Cerebral infarction in sickle cell disease: transcranial Doppler US versus neurologic examination.

PURPOSE: To evaluate flow velocity measurements in the middle cerebral artery (MCA) and/or neurologic examination for detection of cerebral infarction in sickle cell disease (SCD). MATERIALS AND METHODS: Twenty-four pediatric patients aged 6 1/2-17 years with SCD underwent magnetic resonance (MR) imaging, MR angiography, neurologic examination, and transcranial Doppler ultrasonography (US). Transcranial Doppler studies were evaluated for maximum flow velocity in the right and left MCAs. Combinations of cut-off values were used to determine the sensitivity and specificity of transcranial Doppler US for detection of infarction. RESULTS: Neurologic examination had 58% sensitivity and 92% specificity for cerebral infarction. Maximal flow velocity > 200 cm/sec or < 100 cm/sec (including no flow) helped identify nine of 12 patients with infarcts proved at MR imaging, with only one false-positive result (sensitivity, 75%; specificity 92%). The combination of neurologic examination and transcranial Doppler US produced 92% sensitivity and 83% specificity for cerebral infarction. CONCLUSION: The combination of transcranial Doppler US and neurologic examination has potential as a screening technique for infarction in SCD.

Adolescent↗
PubMed1995

Accuracy of neurologic examination and history in detecting evidence of MRI-diagnosed cerebral infarctions in children with sickle cell hemoglobinopathy.

We determined the accuracy of neurologic examination and the history of a previous neurologic event in detecting clinical evidence of a magnetic resonance imaging (MRI)-diagnosed cerebral infarction in 30 children with sickle cell hemoglobinopathy. Each patient had an MRI of the brain, neurologic examination, chart review, and psychometric evaluation. Seventeen children (57%) had MRI evidence of cerebral infarction based on demonstration of parenchymal abnormalities in a vascular distribution. Among the 17 children with MRI evidence of cerebral infarction, only 12 (71%) had an abnormal neurologic examination, and 11 (65%) had a history of a prior neurologic event. In contrast, among the 13 children with normal MRIs, 12 (92%) had normal neurologic examinations, and no child had a previous history of a neurologic event. Multiple, bilateral, heterogeneous cerebral infarctions frequently occur without overt neurologic signs or symptoms in children with sickle cell hemoglobinopathy. Previous studies that relied on a focal neurologic examination or a history of a neurologic event to identify cerebral infarctions in patients with sickle cell hemoglobinopathy most likely underrepresented the true frequency of cerebral infarctions in this population. Future prospective studies of cerebral infarctions in children with sickle cell hemoglobinopathy should include MRIs for identification and classification, rather than neurologic examination or clinical history alone.

Adolescent↗
PubMed1993

Neuropsychologic effects of stroke in children with sickle cell anemia.

We examined the nature and extent of neuropsychologic impairment in children with sickle cell anemia (SCA) with or without stroke. Twenty-nine children with SCA received cranial magnetic resonance imaging. Strokes were classified into three groups: diffuse cortical stroke (n = 11), anterior stroke (n = 6), or none (n = 12). Children with SCA and 20 age-matched sibling control subjects then received a neurologic examination and a neuropsychologic battery of tests that included motor, verbal, spatial, attentional, and memory measures. Tests of spatial function showed that children with diffuse cortical strokes were impaired, whereas children with anterior lesions had intrusions of irrelevant material during list recall. There were no significant differences between children with stroke and sibling control subjects on motor, verbal, or memory measures. Six children had evidence of stroke on magnetic resonance imaging without any history of a damaging neurologic event. These children had impaired neuropsychologic performance relative to that of sibling control subjects in a pattern similar to that of children with overt stroke. Children with SCA without stroke did not differ from sibling control subjects on any measure. Our results indicate that overt and silent strokes result in lesion-specific neuropsychologic deficits in children with SCA.

Adolescent↗
PubMed1991

Setting the optimal erythrocyte protoporphyrin screening decision threshold for lead poisoning: a decision analytic approach.

Erythrocyte protoporphyrin (EP) was introduced in the 1970s as an inexpensive screening test for lead poisoning. As greater knowledge of lead poisoning has accumulated, the recommended EP level at which further evaluation for lead poisoning should be initiated has been lowered from greater than or equal to 50 micrograms/dL to greater than or equal to 35 micrograms/dL. The purpose of this study was to evaluate the utility of this EP threshold. A receiver operator characteristic curve was constructed to assess the relationship between the true-positive rate and false-positive rate of EP at various decision thresholds. The receiver operator characteristic curve was constructed with data from the second National Health and Nutrition Examination Survey from 1976 to 1980, which included 2673 children 6 years of age or younger who had both blood lead and EP level determinations. Decision analysis was then used to determine the optimal EP decision threshold for detecting a blood lead level greater than or equal to 25 micrograms/dL. The receiver operator characteristic curve demonstrated that EP is a poor predictor of a blood lead level greater than or equal to 25 micrograms/dL. At the currently recommended EP decision threshold of 35 micrograms/dL, the true-positive rates and false-positive rates of EP are 0.23 and 0.04, respectively. As a result of the inadequate performance of EP screening for lead poisoning, when the prevalence of lead poisoning is greater than 8%, there is no EP decision threshold that optimizes the relationship between the cost of screening normal children and the benefit of detecting lead-poisoned children. Erythrocyte protoporphyrin measurement is not sufficiently sensitive to be recommended uniformly as a screening test for lead poisoning.

Child↗
PubMedDate not supplied

Influence of penicillin prophylaxis on antimicrobial resistance in nasopharyngeal S. pneumoniae among children with sickle cell anemia. The Ancillary Nasopharyngeal Culture Study of Prophylactic Penicillin Study II.

PURPOSE: To evaluate the consequences of prolonged prophylactic penicillin use on the rates of nasopharyngeal colonization with Streptococcus pneumoniae and the prevalence of resistant pneumococcal strains in children with sickle cell anemia. METHODS: Nasopharyngeal specimens were obtained from children with sickle cell anemia (Hb SS or Hb S beta degrees thalassemia) at 10 teaching hospitals throughout the United States. These patients were participating in a prospective, randomized, placebo-controlled trial in which they were prescribed prophylactic penicillin before their fifth birthday and were randomized to prophylactic penicillin or placebo after their fifth birthday (PROPS II). The specimens were cultured for S. pneumoniae, and isolates were analyzed for antimicrobial susceptibility to nine commonly prescribed antimicrobial agents. RESULTS: Of the 226 patients observed, an average of 8.4 specimens were collected per patient. From 1,896 individual culture specimens, 5.5% of the specimens were positive for S. pneumoniae; 27% of patients had at least one positive culture. Nine percent of the study patients had at least one isolate of penicillin intermediate or resistant pneumococci. There was no significant difference in the percent of positive cultures for S. pneumoniae in those patients given penicillin prophylaxis after 5 years of age (4.1%) compared with those patients given placebo after 5 years of age (6.4%). Likewise, there was no significant difference (p = 0.298) in the percent of patients with at least one positive culture for S. pneumoniae in the group given prophylactic penicillin after 5 years of age (21.8%) compared with the group given placebo after 5 years of age (28.3%). There was no difference between the penicillin and placebo groups in the proportion of patients with penicillin intermediate or resistant pneumococci, but there was a trend toward increased carriage of multiply drug-resistant pneumococci in children > 5 years of age receiving prophylactic penicillin compared to children > 5 years of age receiving placebo. The increased colonization rate with multiply drug-resistant organisms of children > 5 years of age receiving penicillin prophylaxis is not statistically significant. CONCLUSIONS: The potential for continued penicillin prophylaxis to contribute to the development of multiply resistant pneumococci should be considered before continuing penicillin prophylaxis in children with sickle cell anemia who are older than 5 years of age. Added to the published data from PROPS II, which demonstrated no apparent advantage to continue prophylaxis, the data support the conclusion that, for children with no history of invasive pneumococcal disease, consideration should be given to discontinue prophylactic penicillin after their fifth birthday.

Anemia, Sickle Cell↗