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Biomedical subjects

J Charrow

Publications and source records attributed to J Charrow.

At least 19 recordsLinked to original sources
PubMed1998

Gaucher disease: recommendations on diagnosis, evaluation, and monitoring.

BACKGROUND: Timely diagnosis and continued monitoring of patients with type I Gaucher disease is critical because skeletal involvement can permanently disable patients and visceral organ involvement can lead to abdominal pain and secondary hematologic and biochemical complications. OBJECTIVE: To seek clinical consensus for minimum recommendations for effective diagnosis and monitoring of patients with type I Gaucher disease. PARTICIPANTS, EVIDENCE, AND CONSENSUS PROCESS: Contributing authors collaborated in quarterly meetings over a 2-year period to synthesize recommendations from peer-reviewed publications and their own medical experiences. These physicians care for most patients with Gaucher disease in the United States and serve as the US Regional Coordinators for the International Collaborative Gaucher Group Registry, the world's largest database for this disorder. CONCLUSIONS: The definitive method of diagnosis is enzyme assay of beta-glucocerebrosidase activity. Schedules differ for monitoring complications of type I Gaucher disease, depending on symptoms and whether enzyme replacement therapy is used. Hematologic and biochemical involvement should be assessed by complete blood cell count, including platelets, acid phosphatase, and liver enzymes, at baseline and every 12 months in untreated patients and every 3 months and at enzyme replacement therapy changes in treated patients. Visceral involvement should be assessed at diagnosis using magnetic resonance imaging or computed tomographic scans. Skeletal involvement should be assessed at diagnosis using T1- and T2-weighted magnetic resonance imaging of the entire femora and plain radiography of the femora, spine, and symptomatic sites. Follow-up skeletal and visceral assessments are recommended every 12 to 24 months in untreated patients, and every 12 months and at enzyme replacement therapy changes in treated patients.

Bone and Bones↗
PubMed1998

Myelomeningocele and Waardenburg syndrome (type 3) in patients with interstitial deletions of 2q35 and the PAX3 gene: possible digenic inheritance of a neural tube defect.

From a spina bifida clinic we have identified two patients with a syndrome of myelomeningocele and Waardenburg syndrome type 3 (WS3). The patients each possess a single, de novo, interstitial deletion of chromosome 2 (2q35-36.2), including the PAX3 gene. Deletion of PAX3 was confirmed by fluorescence in situ hybridization (FISH). Analysis with PAX3 and flanking microsatellites shows that the deleted interval of chromosome 2 is of paternal origin and is at least 2 and 6 cM in the two patients. Interstitial deletions in this region result in the Waardenburg syndrome (WS1), but have not been associated with neural tube defects (NTDs). Although other etiologies have not been formally excluded, these patients raise the possibility of a digenic etiology of their NTDs via a genetic interaction of the deleted PAX3 gene with a second unidentified locus.

Child, Preschool↗
PubMed1996

Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase.

OBJECTIVES: The incidence and severity of growth retardation in children with type 1 Gaucher disease and the response to enzyme replacement therapy with alglucerase were studied. STUDY DESIGN: A retrospective analysis of growth in 99 children and adolescents with type 1 Gaucher disease before treatment, and in 54 of those subjects during treatment, was done. Growth was compared with gender, age, and dosage of replacement enzyme. RESULTS: Linear growth was normal in the first 1 to 2 years of life and then decelerated. Height was at or below the 5th percentile in 50% of all subjects immediately before treatment. The mean z score was -1.49 (95% confidence interval, -1.83 to -1.16), corresponding to the 6.8th percentile for height. Seventy-two percent were below the 50th percentile and 50% were at or below the 5th percentile for mid-parental height (p <0.001). One and one-half years after treatment was started, the estimated mean z score for all subjects was -1.01, which corresponds to the 16th percentile for height. Normal growth was achieved within 4 to 30 months in eight of nine subjects who were at or below the 5th percentile. It occurred only in those receiving higher doses (60 to 120 U/kg per 4-week period) of alglucerase. There was a significant association between z scores for height before treatment and liver enlargement (r= 0.57; p < 0.01). CONCLUSIONS: Half of the subjects who manifest type 1 Gaucher disease in childhood have growth retardation. Treatment with adequate amounts of modified enzyme replacement was effective in normalizing linear growth.

Adolescent↗
PubMed1995

Optic pathway tumors in children: the effect of neurofibromatosis type 1 on clinical manifestations and natural history.

OBJECTIVE: To distinguish the clinical manifestations and natural history of optic pathway tumors (OPT) associated with neurofibromatosis type 1 (NF-1 OPT) from that of OPT not associated with NF-1 (non-NF-1 OPT). METHODS: Two groups of children with OPT were compared: (1) 17 children with NF-1 OPT who were followed prospectively, and (2) 19 children with non-NF-1 OPT who were identified retrospectively by a review of medical records. RESULTS: Precocious puberty was a common initial sign in the children with NF-1 OPT (5/17), and was not found in any patients without NF-1. In contrast, children with non-NF-1 OPT had symptoms attributable to increased intracranial pressure (12/19 and nystagmus (5/19); these symptoms were not found in any patient with NF-1. Decreased visual acuity at the time of diagnosis was common in both groups. There was no significant difference between the children with NF-1 OPT and those with non-NF-1 OPT as to age at diagnosis or sex distribution. Optic nerve involvement was more common in NF-1 (p < 0.001). Both isolated and bilateral optic nerve tumors were found exclusively in children with NF-1, whereas chiasmal (p = 0.016) and optic tract involvement (p = 0.001) were more common in those with non-NF-1 OPT. Radiographic evidence of hydrocephalus was found in none of the children with NF-1 OPT compared with 79% of the non-NF-1 OPT group. Progressive disease was seen in 12% of patients with NF-1 OPT compared with 63% of those with non-NF-1 OPT. CONCLUSIONS: Differences exist between NF-1 OPT and non-NF-1 OPT both at the time of diagnosis and during follow-up. Optic pathway tumors caused by NF-1 and non-NF-1 OPT have different biologic properties that distinguish both their initial clinical manifestations and their natural history.

Astrocytoma↗
PubMed1995

Precocious puberty in children with neurofibromatosis type 1.

We undertook a comprehensive study of children with neurofibromatosis type 1 (NF-1) cared for in a large multidisciplinary clinic to determine the prevalence of precocious puberty and its relationship to optic pathway tumors (OPTs). Precocious puberty was diagnosed in 7 of 219 children with NF-1 (5 boys and 2 girls) examined between Jan. 1, 1985, and April 20, 1993. All seven children had OPTs involving the optic chiasm; they represented 39% of children with NF-1 and chiasmal tumors (95% confidence interval, 17% to 64%). Eleven prepubertal children (aged 2 to 10 years) with NF-1 and OPTs, and age- and sex-matched NF-1 control subjects without OPTs, underwent luteinizing hormone-releasing hormone (LH-RH) stimulation tests. Two boys with OPTs had pubertal luteinizing hormone (LH) responses, and testosterone levels > 10 ng/dl. Basal LH levels were also elevated in these two boys when tested with a very sensitive immunochemiluminometric assay. None of the children without an OPT had either a pubertal response to LH-RH or an elevated basal LH level. We conclude that precocious puberty in children with NF-1 is found exclusively in those who have OPTs involving the optic chiasm; it is a common complication in those children. With the use of a highly sensitive LH assay, biochemical evidence of hypothalamic-pituitary-gonadal axis activation may be demonstrated, even without provocative testing.

Child↗
PubMed1994

Natural history of optic pathway tumors in children with neurofibromatosis type 1: a longitudinal study.

To assess the natural history of optic pathway tumors (OPT) in children with neurofibromatosis type 1 (NF-1), from January 1985 through May 1993 we performed a prospective, longitudinal study of OPT in an unselected population of children with NF-1. Of 227 children with NF-1 seen in a specialty clinic, 176 (77%) underwent neuroimaging. Children in whom tumors were identified were followed closely by both repeated neuroimaging and ophthalmologic examinations to detect tumor growth or visual deterioration. Thirty-three children (19%) were found to have OPT at a median age of 4.2 years. The median age of children who had ophthalmologic complaints was significantly lower than that of children who had no such complaints (1.9 vs 5.3 years; p < 0.001). Although eight tumors were discovered because of ophthalmologic complaints or evidence of precocious puberty, 25 children (76%) were free of symptoms at the time of diagnosis. Twenty-one children (64%) had normal ophthalmologic findings at diagnosis; six children, all with chiasmal tumors, had previously unrecognized decreased visual acuity. Only three children (9%) had evidence of either tumor growth or deteriorating vision after diagnosis; the median duration of neuroimaging follow-up was 2.4 years (range, 0.2 to 7.2 years) and of ophthalmologic examinations 3.4 years (range, 0.2 to 8.1 years). All symptomatic OPT were diagnosed before 6 years of age. We conclude that OPT rarely progress during the next few years in children with NF-1 once the OPT have been discovered. The utility of screening neuroimaging for OPT in symptom-free children with NF-1 appears very limited.

Adolescent↗
PubMed1993

Autosomal dominant multiple café-au-lait spots and neurofibromatosis-1: evidence of non-linkage.

Multiple café-au-lait spots have been observed in successive generations of several families without any other manifestations of neurofibromatosis (NF) or any other systemic disorder. The café-au-lait spots in these families segregate as an autosomal dominant trait. The relationship (if any) between the gene for this trait and the NF-1 gene has previously been unknown. We describe a family with five individuals spanning four generations with dominantly inherited café-au-lait spots, without any other stigmata of NF-1. Linkage analysis with probes proximal, distal, and within the NF-1 gene indicate that the trait in this family is not linked to NF-1. We propose that this condition be called Familial Café-Au-Lait Spots (FCAL) to distinguish it from the neurofibromatosis syndromes.

Alleles↗
PubMed1993

Black clouds. Work load, sleep, and resident reputation.

OBJECTIVE: Although it is assumed that residents in a specific training program will have comparable experiences, residents commonly perceive that some have consistently more difficult times on call. Such residents in our program are said to have "black clouds." We sought to determine if these perceptions were related to differences in real work load. METHODS: We collected data about the on-call experiences of our first-year pediatric residents (PL-1s) for 358 days (1355 on-call experiences) during the 1984-1985 academic year. Every PL-1 (n = 19) reported the following data the morning after each night on call: hours of sleep, number of admissions, total number of patients, number of deaths, number of transfers to the pediatric intensive care unit, number of delivery room trips, and a subjective assessment of work load, using a three-point scale. The reputation of each house officer was determined by asking all residents in the program (PL-1s, PL-2s, and PL-3s) to rate each other three times during the year regarding how hard they worked on call. RESULTS: There were significant differences among PL-1s in how difficult they perceived their work load to be and in how much they slept (P < .001 using analysis of variance). However, actual work load (as measured by the number of either admissions or patients) did not vary significantly among the residents. There was a strong negative association between self-perception of work load and hours of sleep (r = -.75; 95% confidence interval, -0.73 to -0.76). Sleep was the major predictor of perceived work load (multiple R2 = .563 using multiple linear regression analysis). The absence of an association between perceived and actual work load is attributed to large differences in the residents' working styles. This is evidenced by a wide range of correlations among PL-1s between the number of admissions and hours of sleep (range of r values, -.66 to -.16). A reputation for difficult on-call experiences was strongly associated with few hours of sleep (r = -.77; 95% confidence interval, -0.49 to -0.91), but not with actual work load measured by the number of admissions, patients, deaths, or other variables. Sleep was the major predictor of reputation (multiple R2 = .567 using multiple linear regression analysis). CONCLUSIONS: Some residents did have a black cloud; they slept less, perceived that they worked harder than average, and had a reputation for having difficult on-call experiences. Residents with a black cloud function differently from their colleagues; for example, some may be inefficient, while others may create extra work for themselves. Residency program directors must recognize these functional differences to effectively evaluate and counsel house officers.

Analysis of Variance↗
PubMed1993

Carboplatin-induced regression of an optic pathway tumor in a child with neurofibromatosis.

Optic pathway tumors are common in children with neurofibromatosis-1 (NF-1). The optimal management of these tumors is unknown, particularly when the optic chiasm and other brain structures are involved. We report the dramatic response to carboplatin in a 10-year-old girl with NF-1 and a progressive optic pathway tumor. Tumor shrinkage was accompanied by striking improvement in visual fields, return of color discrimination, and marked improvement in visual acuity. No significant toxicity was observed. One year following completion of chemotherapy the glioma remains as small or smaller than it was at the conclusion of therapy, and there has been no deterioration of vision. Carboplatin is a promising agent for the treatment of optic pathway tumors in children with NF-1.

Carboplatin↗
PubMed1993

Surgical treatment of patients with lobar holoprosencephaly: a personal note.

The diagnosis of holoprosencephaly usually implies a poor prognosis and is often regarded as a contraindication for surgical correction of associated clefts of the lip or palate. Between 1985 and 1991, 4 patients with lobar holoprosencephaly were evaluated and studied with computed tomography or magnetic resonance imaging. All had cleft palate and 3 had paramedian cleft lip; all 4 exhibited some degree of nasal dysplasia. All patients are presently alive, at a mean age of 26.6 +/- 2.4 months (mean +/- SD). Three of the children showed normal or near normal development, whereas the fourth was severely retarded. Our experience suggests that some children with lobar holoprosencephaly have a highly variable degree of intellectual development and that long-term survival may be expected.

Agenesis of Corpus Callosum↗
PubMed1992

Emergence of optic pathway gliomas in children with neurofibromatosis type 1 after normal neuroimaging results.

We report the appearance of gliomas of the optic nerve or chiasm in four young children with neurofibromatosis type 1 whose previous neuroimaging studies showed no abnormalities; the age range of the children was 1 year 8 months to 5 years 9 months at the time the tumors were detected. Normal neuroimaging findings in an infant or young child with neurofibromatosis type 1 does not provide assurance that the optic nerves and chiasm will remain healthy.

Child, Preschool↗
PubMed1991

Autosomal recessive cerebellar hypoplasia and endosteal sclerosis: a newly recognized syndrome.

We describe a brother and sister and an unrelated boy with congenital cerebellar hypoplasia and endosteal sclerosis. All 3 children presented with ataxia and developmental delay, and were found to have microcephaly, short stature, oligodontia, strabismus, nystagmus, and congenital hip dislocation. A previously published case is reviewed. The disorder appears to represent a newly recognized autosomal recessive syndrome.

Cerebellum↗
PubMed1990

When is a test result abnormal? Defining limits and risks.

Test results from "normal" and "non-normal" individuals frequently overlap. Individuals with test results near the region of overlap have a high risk of being misdiagnosed. We present a statistical method for quantifying the certainty of diagnoses and defining a normal range, and illustrate its application with a specific example from a Tay-Sachs disease carrier screening program. This method can be applied to any test result based on a continuous variable and is particularly well suited to screening programs where the risk or incidence of a disease is known. We use an inconclusive range to reduce the likelihood of incorrect diagnoses resulting from measurement error and borderline results. The limits of the normal, inconclusive, and nonnormal ranges are based on three considerations: (1) the probability of misdiagnoses, (2) the expected frequency of inconclusive diagnoses, and (3) the reproducibility of the test results.

Bayes Theorem↗
PubMed1989

Optic gliomas in children with neurofibromatosis type 1.

To determine the frequency and natural history of tumors of the optic nerves and chiasm in patients with neurofibromatosis type 1, we obtained computed tomographic scans of 65 children who had no known visual or ocular abnormalities before their initial evaluation. Optic gliomas were detected in 10 children (15%). The median age of children with gliomas was 4.3 years (mean 5.8 years, range 9 months to 21 years). Three children (30%) had isolated, unilateral tumors, three (30%) had bilateral tumors, and four (40%) had involvement of the optic chiasm and of one or both nerves. Definite abnormalities of vision were found in only two children (20%). Five additional children were referred to the clinic after evaluation of ophthalmologic complaints led to the diagnosis of neurofibromatosis type 1: three had unilateral exophthalmos and two had plexiform neurofibromas of the eyelid with associated glaucoma. Ipsilateral optic gliomas were found in all five children; one child also had a contralateral tumor. Optic gliomas are commonly identified in young children with neurofibromatosis type 1 who have no ocular or visual abnormalities. Optic nerve gliomas may be associated with plexiform neurofibromas of the eyelid and glaucoma.

Adolescent↗
PubMed1988

Biochemical abnormalities in rhizomelic chondrodysplasia punctata.

Biochemical studies with emphasis on peroxisomal functions were conducted in six patients with well-documented rhizomelic chondrodysplasia punctata (RCDP) and compared with findings in patients with Zellweger syndrome and neonatal adrenoleukodystrophy (ALD). Patients with RCDP had three characteristic biochemical abnormalities: (1) profound defect in plasmalogen (ether lipid) synthesis, which is significantly greater than the analogous defect in Zellweger syndrome or neonatal ALD; (2) reduction of phytanic acid oxidation activity to 1% to 5% of control, similar to that observed in Refsum disease, Zellweger syndrome, and neonatal ALD; (3) presence of the unprocessed form of peroxisomal 3-oxoacyl-coenzyme A thiolase in the postmortem liver of two patients. Other peroxisomal functions were normal, including levels of very long chain fatty acids, pipecolic acid, and bile acid intermediates, and immunoblot studies of peroxisomal acyl-CoA oxidase and bifunctional enzyme in postmortem liver. Unlike what is observed in Zellweger syndrome and neonatal ALD, catalase activity in cultured skin fibroblasts was sedimentable, indicating that peroxisome structure is not grossly deficient in RCDP. The biochemical abnormalities in RCDP were consistent and set it apart from all the other known peroxisomal disorders.

Acetyl-CoA C-Acyltransferase↗