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Biomedical subjects

B L Maria

Publications and source records attributed to B L Maria.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparative value of thallium and glucose SPECT imaging in childhood brain tumors.

Thallium-201 chloride (201Tl) single-photon emission computed tomography (SPECT) detects a high percentage of histologically and anatomically diverse pediatric brain tumors. Thallium-201 chloride SPECT and F-18 fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) are the most commonly used radionuclide techniques in neuro-oncology. Having developed a methodology to image 18F-FDG with SPECT, the authors performed SPECT scans coupled with magnetic resonance imaging to assess the comparative sensitivity of 201Tl and 18F-FDG in 19 children with brain tumors. Tumors were detected using 201Tl SPECT in 14 of 19 patients. Five of five postoperative residual tumors were detected by 201Tl SPECT, and six of seven after irradiation recurrences were detected. F-18 fluoro-deoxy-glucose SPECT detected tumors in only three of 19 patients, all of whom had abnormal 201Tl studies (all three after therapy recurrences). Thallium-201 chloride SPECT could be interpreted in 18 of 19 patients without magnetic resonance imaging confirmation, but none of the 19 18F-FDG SPECT studies could be interpreted without magnetic resonance imaging. Thallium-201 chloride SPECT is more sensitive than 18F-FDG SPECT in the detection of primary or recurrent childhood brain tumors. The failure of 18F-FDG SPECT in follow-up after therapy is primarily a problem of limited fluoro-deoxy-glucose uptake, not spatial resolution. Thallium-201 chloride SPECT is a promising imaging modality in neuro-oncology.

Brain Neoplasms↗
PubMed1998

Neurobehavioral development in Joubert syndrome.

Research on children with Joubert syndrome has focused on brain structural abnormalities and associated clinical symptoms. The degree of developmental delay has not been objectively reported. We investigated the neurobehavioral development of children with Joubert syndrome through neurobehavioral assessment in the largest sample to date. Thirty-two parents of children with Joubert syndrome completed the Child Development Inventory and magnetic resonance imaging (MRI) data was gathered on 17 of these children. Results indicate that 94% were severely impaired according to the Child Development Inventory, with age being positively correlated with degree of neurobehavioral impairment. The average developmental age of our sample was 19 months (63% below chronological age). Severity of illness as measured by the General Development scale of the Child Development Inventory and severity of illness as measured by MRI (overall severity rating) did not yield consistent data regarding severity of the midbrain and cerebellar malformations. Similarly, markers of abnormal cerebral development such as cortical atrophy and delayed myelination were independent of severity of illness ratings on the Child Development Inventory. The degree of developmental delay in Joubert syndrome and the severity of gross central nervous system malformations appear independent.

Adolescent↗
PubMed1998

High prevalence of bihemispheric structural and functional defects in Sturge-Weber syndrome.

Abnormal cerebral venous drainage is associated with hypoxia and glucose deprivation, which can account for progressive neurologic deterioration in Sturge-Weber syndrome. Although developmental delay is common in Sturge-Weber syndrome, bihemispheric calcification is uncommon. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to study the neuroanatomy, while single photon emission computed tomography (SPECT) was used concurrently to evaluate perfusion and glucose metabolism using 99mTc hexamethylpropyleneamine oxime (HMPAO) and [18F] fluorodeoxyglucose (FDG), respectively. Ten patients (10 to 22 years of age) with previously diagnosed Sturge-Weber syndrome, port-wine nevi, and clinical evidence of seizures or stroke-like episodes were studied. Five children with onset of seizures in the first year of life had overall clinical severity comparable to that of children with later-onset seizures. Calcification was present in both hemispheres in one patient; six additional patients had other radiologic evidence of bihemispheric disease; SPECT studies detected bihemispheric disease in four cases. Our study is the first to concurrently evaluate structure, perfusion, and glucose metabolism in Sturge-Weber syndrome and to show a mismatch between functional and structural brain imaging in both cerebral hemispheres. Widespread abnormalities of cerebral perfusion and glucose metabolism might explain the high prevalence of developmental delay associated with Sturge-Weber syndrome. Longitudinal studies are needed to define better the natural history of neurologic deterioration and radiologic progression that relates to central nervous system circulatory dysfunction in Sturge-Weber syndrome.

Adolescent↗
PubMed1998

Central nervous system structure and function in Sturge-Weber syndrome: evidence of neurologic and radiologic progression.

Sturge-Weber syndrome is characterized by the presence of a port-wine nevus, epilepsy, stroke-like episodes, headache, and developmental delay. We studied 20 cases to test the hypothesis that decreased cerebral blood flow alters neurologic function by affecting cellular glucose metabolism. Group A consisted of 10 patients with a mean age of 1.75 years and early seizure onset (6.8 months), whereas group B was composed of older patients (mean age, 15.3 years) with later onset of seizures (3.7 years). Neurologic disease was more severe in group A, but group B had more widespread structural brain defects - shown on computed tomographic scans and magnetic resonance imaging - and metabolic brain defects shown on hexamethylpropyleneamine oxime and [18F] fluorodeoxyglucose single photon emission computed tomographic scans. Six group A cases had hypoperfusion at baseline and five of nine had worsening of perfusion and glucose metabolism 1 year later. A total of 119 stroke-like episodes occurred in six group A cases and eight group B cases; there were 65% fewer strokes in children treated with aspirin. The data suggest that progressive hypoperfusion and glucose hypometabolism are associated with neurologic deterioration in Sturge-Weber syndrome. Longitudinal studies are needed to better define the natural history of disease and to evaluate the safety and efficacy of aspirin therapy.

Adolescent↗
PubMed1997

Gene therapy for pediatric brain tumors.

There have been impressive surgical, radiotherapeutic, and chemotherapeutic advances in treating cancer. However, the outlook for patients with malignant brain tumors is still dismal. Gene therapy offers hope of replacing defective genes, amplifying the immune response to cancer, and sensitizing tumor cells to systemic therapies (suicide gene therapy). The insertion of the thymidine kinase gene from herpes virus (HSV-TK) into glioma cells can sensitize them to intravenous ganciclovir. Pivotal to the HSV-TK strategy is the "bystander effect," which results in a larger number of tumor cells being killed than those that have been genetically altered. The presence of gap junctions between tumor cells and immunocompetence are required experimentally to observe the "bystander effect." At present, clinical trials using suicide gene therapy in newly diagnosed and recurrent gliomas are underway. Suicide gene therapy faces many challenges in neuro-oncology until p53 gene replacement and immunomodulatory strategies become feasible.

Brain Neoplasms↗
PubMed1997

Gene therapy for neurologic disease: benchtop discoveries to bedside applications. 1. The bench.

The overall goal of this review is to provide the pediatric neurologist with a theoretical foundation in gene therapy. Gene therapy became feasible in the early 1970s and the first transfer of a foreign gene into humans was approved by the NIH in 1989. Adenovirus, adeno-associated virus, herpes-simplex virus, retroviruses, and other vectors have been used to efficiently transduce genes into cells in vitro and in vivo. We discuss laboratory experiments that have provided a strong scientific rationale for implementing human clinical trials of gene therapy for neurologic malignancy. The development of viral and nonviral vectors that mediate efficient gene insertion into human cells has created the prospect of using gene therapy for cancer or brain disease. The NIH has approved more than 100 gene therapy protocols since 1989. However, the field will require more research on gene delivery systems before gene therapy becomes an established therapeutic strategy for an array of central nervous system diseases.

Animals↗
PubMed1997

Gene therapy for neurologic disease: benchtop discoveries to bedside applications. 2. The bedside.

Important advances in basic research have made it possible to examine the safety, toxicity, and efficacy of gene therapy in humans for over 5 years. The development of sophisticated gene delivery systems has resulted in approval by the Recombinant DNA Advisory Committee (RAC) of 125 gene therapy or gene marking studies. One of the primary applications of current retroviral-mediated gene insertion technology has been for malignant brain tumors. Studies are therefore underway to examine the efficacy of "suicide" gene therapy in children with recurrent brain tumors and adults with newly diagnosed or recurrent gliomas. Since a high proportion of genetic disorders produce neurologic dysfunction, gene therapy is likely to impact the management of neurologic disease in the foreseeable future. Patients with human immunodeficiency virus (HIV), Gaucher's disease, and Hunter syndrome are now enrolled in gene therapy trials. It will be challenging for the child neurologist to stay abreast of rapid developments in the field of gene therapy. By participating in the design and implementation of clinical trials in gene therapy, the neurologist may reduce the intense toll that several neurologic diseases take on children and their families.

Adult↗
PubMed1997

Correlation between gadolinium-diethylenetriaminepentaacetic acid contrast enhancement and thallium-201 chloride uptake in pediatric brainstem glioma.

We previously showed that thallium-201 (201Tl) chloride is accumulated in over 75% of brain tumors, including brainstem gliomas. The imaging of 201Tl with single photon emission computed tomography (SPECT) may require an abnormal increase in permeability of tumor vessels to allow penetration of the blood-brain barrier. To test this hypothesis, we evaluated the correlation between gadolinium enhancement and the degree of 201Tl uptake on SPECT and the contributions of either gadolinium enhancement or 201Tl uptake to the prognosis in children with brainstem gliomas. Forty-two sets of paired SPECT scans and magnetic resonance imaging (MRI) scans were obtained longitudinally in 13 cases. Altogether, 31 of 42 pairs (74%) of scans showed concordance between the presence of gadolinium enhancement and 201Tl uptake. There were no cases that demonstrated 201Tl uptake but lacked gadolinium enhancement. The results indicate that 201Tl SPECT is of value primarily when brainstem tumors have vessels that are demonstrably permeable to gadolinium, prior to or as a result of radiotherapy.

Adolescent↗
PubMed1997

"Joubert syndrome" revisited: key ocular motor signs with magnetic resonance imaging correlation.

Joubert syndrome is characterized by episodic hyperpnea and apnea, developmental delay, hypotonia, truncal ataxia, ophthalmologic abnormalities, and vermian dysgenesis. We studied 15 patients with the diagnosis of Joubert syndrome to (1) more fully define the syndrome's clinical features, and (2) correlate the clinical features with magnetic resonance imaging (MRI) findings. Eight of 15 patients had a history of episodic hyperpnea and apnea. All patients had developmental delay and hypotonia. Of the 13 patients receiving detailed neuro-ophthalmologic evaluations, three had optic nerve dysplasia, pendular nystagmus, and gaze-holding nystagmus. All 13 patients had a normal vestibulo-ocular reflex based on head thrust, but had absent to poor ability to cancel the vestibulo-ocular reflex horizontally and vertically. Twelve of 13 patients had impaired smooth pursuit. Twelve of 13 patients had defects in initiation of saccades and quick phases. Two of the most consistent radiologic features were absent or hypoplastic posterior cerebellar vermis, and deformed midbrain and pontomesencephalic junction, which based on ocular motor physiology correlate with the vestibulo-ocular reflex cancellation/ pursuit defect and saccade initiation defect, respectively. As a result of midbrain, vermian, and superior cerebellar peduncle abnormalities, axial neuroimaging showed a unique "molar tooth" appearance of these structures. These results indicate that Joubert syndrome results from maldevelopment of the midbrain and cerebellar vermis, producing a pathognomonic sign on MRI.

Adolescent↗
PubMed1997

Medicine and money: an approach to compensating university physicians.

Academic medical centers have been restructuring faculty compensation plans because decreasing clinical revenues have created budgetary problems. We propose an overall compensation strategy designed to reward high performance of university physicians. The approach incorporates Management by Objectives to improve communication of expectations within the organization and provide college of medicine leadership with much needed mechanisms to align faculty compensation with productivity.

Academic Medical Centers↗
PubMed1996

Assessment of laminin-mediated glioma invasion in vitro and by glioma tumors engrafted within rat spinal cord.

Cell motility within central nervous system (CNS) neuropil may be largely restricted yet infiltration by glioma cells is commonly observed. Glioma cells remodel nervous tissue and may assemble extracellular matrix in order to migrate. We examined the rat C6 glioma cell line for laminin expression and response in vitro and following engraftment into rat spinal cord. C6 cell cultures expressed laminin-2. C6 cells attached equally well to substrates of purified laminin-1 and laminin-2 and laminin-2-enriched C6 conditioned medium. In contrast, C6 cell migration was substantially greater on laminin-2 and C6-derived substrata than on laminin-1. Glioma cell attachment to laminin-1 and -2 was largely inhibited by antibody to the laminin receptor LBP110 and by an IKVAV peptide but not by YIGSR or control peptides. IKVAV peptide and anti-LBP110 antibodies also inhibited glioma cell invasion through synthetic basement membrane. Anti-beta 1 integrin antibody selectively inhibited cell migration and invasion on laminin-2 substrata without affecting percent cell attachment. These findings suggest C6 cell migration and invasion are promoted by autocrine release of laminin-2 and involve LPB110 and beta 1 integrin laminin receptors. A possible role for laminin-2 in CNS infiltration in vivo was examined following glioma engraftment into rat spinal cord. Engrafted C6 tumors share many histologic features of invasive human glioma. Engrafted glioma cells expressed laminin, LBP110 and beta 1 integrin antigens, indicating the molecular mechanisms of C6 motility observed in culture may contribute to glioma invasion in vivo. NMR and corroborative immunocytochemistry provided precise means to monitor tumor progression following glioma engraftment into rat spinal cord. Advantages of this glioma model are discussed regarding the assessment of anti-adhesive therapies in vivo.

Animals↗
PubMed1996

Altered cognitive functioning in children with idiopathic epilepsy receiving valproate monotherapy.

Once a child is diagnosed with epilepsy, a primary concern is whether or not the child's behavior and cognitive abilities will be affected by the disease, by the drug prescribed for seizure control, or both. Direct cognitive effects by the epileptic condition have been described. On the other hand, cognitive effects in epilepsy have been attributed to antiepileptic drug therapy. Valproate is an antiepileptic drug of choice in managing the commonest childhood epilepsy syndromes. Although frequently prescribed in pediatric neurology practice, there have been relatively few studies investigating the cognitive effects of valproate therapy in children. Cognitive effects of valproate reported in normal adult volunteers and in adults with epilepsy cannot be generalized to the pediatric population. The results of investigations on children are less conclusive. Guidelines for antiepileptic drug trials in children have recently been formulated. Carefully designed studies are required in determining the cognitive effects of valproate in the pediatric population. Neuropsychological measures that are likely to assess subtle changes in higher brain functions crucial to learning in children should be employed. We propose a test battery to assess for cognitive changes associated with anticonvulsant therapy in children.

Anticonvulsants↗
PubMed1994

High-dose chemotherapy with marrow reinfusion and hyperfractionated irradiation for children with high-risk brain tumors.

Between November 1990 and March 1993, nine pediatric patients with newly diagnosed brain tumors having a high risk of failure with standard treatment received high-dose thiotepa/cyclophosphamide chemotherapy followed by autologous bone marrow infusion and involved-field hyperfractionated radiation therapy. The presenting diagnoses were brainstem glioma (BSG) [6], parietal mixed high-grade oligodendroglioma-astrocytoma [1], thalamic anaplastic astrocytoma [1], and high-grade parietal glioma [1]. Following chemotherapy there were two partial responses, one minor response, three with stable disease, and one with progressive disease. Responses were not evaluated in two patients who had toxic deaths. Following radiation two patients, one with brainstem glioma and one with anaplastic mixed glioma, achieved complete remission. The overall survival is no better than conventional therapy.

Adolescent↗
PubMed1994

Value of thallium-201 SPECT imaging in childhood brain tumors.

Thallium-201 chloride single photon emission computed tomography (201Tl SPECT) has been proposed as a diagnostic tool in the assessment of patients with brain tumors. We performed SPECT scans coupled with magnetic resonance imaging (MRI) in children with brain tumors to determine the sensitivity and potential value of SPECT in neuro-oncology. Each patient was injected with 2.5-3.0 mCi of thallium chloride, followed by technetium-99m HMPAO (5-15 mCi) to assess cerebral perfusion. 201Tl uptake was imaged with triple-headed SPECT in 20/24 (83%) histologically and anatomically diverse neoplasms with MRI-measurable residual disease, including 13/16 (80%) posterior fossa tumors. 201Tl SPECT demonstrated uptake in tumors with MRI volumes ranging from 0.03 to 60 cm3. 201Tl SPECT imaging was not correlated with the following MRI features: gadolinium enhancement, necrosis, exophytic, unicentric and multicentric. 201Tl uptake was not detectable in patients with tumors of maldevelopmental origin or radionecrosis. It is suggested that 201Tl SPECT is an important imaging adjunct in the assessment of children with brain tumors.

Adolescent↗
PubMed1994

XNEOr: development and evaluation of an expert system to improve the quality and cost of decision-making in neuro-oncology.

The treatment of brain tumors requires a large team of medical experts. However, the process of medical decision-making for these patients is hampered by the frequent inaccessibility of the experts because of conflicting scheduling, inconsistencies in the management of different patients, and the fact that multiple experts often yield multiple opinions. The goals of this work were (1) to develop and validate an expert system to assist the medical team deliver efficient, quality care to children with recurrent medulloblastoma, a common type of pediatric brain tumor, and (2) to determine if the expert system can be used as an educational tool. The results of our study indicate that residents enjoy learning by using XNEOr, the brain tumor expert system. XNEOr enabled residents to order appropriate ancillary tests for patients and to make fewer incorrect treatment decisions. The potential net effect of residents using XNEOr may be increased patient and family satisfaction and decreased probability of medical liability. At a time of important changes in our health care system, novel expert systems hold promise as tools to reduce medical costs, improve the quality of multi-expert medical care, and advance health care education.

Brain Neoplasms↗
PubMed1993

Quantitative methods for scoring cell migration and invasion in filter-based assays.

The ability of cells to traverse pores in a biocompatible filter provides means for examining cell chemoattraction. Filter-based assays also permit rapid, quantitative assessment of the in vitro migratory and invasive potential of tumor cells. Scoring migration has relied on visual counting of stained cells which appear on the underside of the filter and determining a true percentage score involves arduous counting of cells on both filter surfaces. Visual counting of random fields may be unreliable, and counting all fields is laborious. In the present study we developed and compared two alternative methods for scoring cell numbers in filter-based assays, a colorimetric assay of toluidine blue binding, and a radioassay of cells prelabeled with [3H]thymidine. Each method was evaluated for sensitivity, variability, ease of use and efficiency, and suitability for use in assays of cell migration and invasion. The radiolabeling method proved to be sensitive and reliable and was the most efficient technique. Although less sensitive and specific, the colorimetric dye method offered a rapid and reliable, nonradioactive alternative with the distinct advantage of preserving intact cultures for follow-up visual assessments. We conclude that colorimetric and radiolabel scoring of filter-based assays are reliable and efficient semiautomated methods which provide means to obtain more complete assessments of cell migration and invasion.

Cell Count↗
PubMed1993

The prevalence of neurologic dysfunction in children with strabismus who have superior oblique overaction.

BACKGROUND: Children with certain neurologic diseases (hydrocephalus, meningomyelocele, or cerebral palsy) have been reported to manifest a high frequency of A-pattern strabismus and superior oblique overaction. However, it is not generally recognized whether children with strabismus who have superior oblique overaction are more likely to have concurrent neurologic diseases than those without superior oblique overaction. In this study, the authors examine this issue. METHODS: The authors retrospectively reviewed the medical records of all patients (n = 168) with overdepression of the downturned eye in adduction, who were examined between October 1989 and March 1992. A randomly selected population of children with strabismus who did not have overdepression of the eye on infraduction and adduction served as controls (n = 98). Patients with simulating or confounding conditions such as pseudo-superior oblique overaction, inferior rectus skew deviation (alternating skew on lateral gaze), and restrictive or paralytic strabismus, and who were older than 20 years of age, were excluded. RESULTS: One hundred twelve patients with true superior oblique overaction were analyzed. Of these 112 patients, 45 (40.2%) had concurrent neurologic abnormalities, compared with less than one fifth (17.3%) of control subjects (17 of 98) (P < or = 0.001). CONCLUSIONS: Children with strabismus who have superior oblique overaction were found to have higher prevalence of concurrent neurologic diseases than control subjects. Superior oblique overaction may represent a clinical marker for an associated neurologic dysfunction, possibly representing a form of skew deviation in some cases.

Adolescent↗