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Biomedical subjects

C Raffel

Publications and source records attributed to C Raffel.

At least 55 records · Page 3Linked to original sources
PubMed1994

Tumoral invasion in the central nervous system.

During growth, migration and differentiation, cells closely interact with the extracellular matrix (ECM). The harmony between cells and their environment is a key factor that maintains the normal architecture of tissues. Loss of growth control is not the only characteristic of oncogenesis, loss of control by the ECM is an important event that allows malignant cells to further progress toward invasion and metastasis. Changes in cell adhesion, proteolytic degradation of the ECM and cell migration have all been described during invasion of most tissues by tumor cells. However little is known of these changes in tumors of the central nervous system (CNS). Although brain tumor cells may share some of the invasive characteristics of tumors that arise outside the CNS, the particular structure and composition of the brain ECM suggest the existence of unique invasive mechanisms in these tumors. Furthermore, the interaction between brain tumor cells and their ECM may explain the intriguing observation that despite their highly invasive behavior, these cells remain poorly metastatic. This review focuses on biochemical mechanisms essential for tumor invasion and how they relate to invasion of tumors that arise in the CNS.

Animals↗
PubMed1994

Subcutaneous palisading granuloma of the scalp in childhood.

Subcutaneous palisading granulomas, lesions characterized by collagen necrosis and chronic inflammatory changes, may present as ill-defined, immobile, nontender masses of the scalp. They are frequently multiple and may vary in size over time. Imaging studies rarely show involvement of the calvarium. The histological pattern of palisading histiocytes around necrobiotic granulomas is seen in association with a variety of systemic illnesses but more commonly occurs as an isolated entity in childhood. They are unlikely to herald rheumatological disease unless the erythrocyte sedimentation rate is elevated. In the presence of juvenile rheumatoid arthritis, histological confirmation is usually not indicated. If the lesions are not associated with any other clinical symptoms excisional biopsy may be indicated to establish a diagnosis. The nodules need not be removed as they will spontaneously regress.

Child, Preschool↗
PubMed1994

The lack of a role for p53 in astrocytomas in pediatric patients.

Mutations in the p53 gene, which codes for a cell division regulatory protein, have been identified in approximately one-third of adult astrocytomas. We evaluated 35 astrocytic tumors (17 pilocytic, 4 diffuse low grade, 12 anaplastic, and 2 glioblastoma) in pediatric patients for p53 mutations, using polymerase chain reaction-single-stranded conformation polymorphism analysis as a screening technique. Additionally, those tumors identified with homozygosity in the area of the p53 gene on chromosome 17 by Southern blotting were sequenced to look for p53 mutations. No tumors were identified with polymerase chain reaction-single-stranded conformation polymorphism analysis shifts indicative of mutations in the p53 gene. Five of 21 tumors were homozygous in the region of the p53 gene on chromosome 17; no mutations in exons 5 to 8 were found in any of these tumors. The frequency of p53 mutation in pediatric astrocytomas is significantly less than the frequency for adult tumors, regardless of tumor grade. Furthermore, the frequency of p53 mutations in high-grade astrocytomas is significantly lower in pediatric tumors than in adult tumors. These results suggest that p53 is not important in the oncogenesis of pediatric astrocytomas. Oncogenesis in pediatric astrocytomas may occur by different mechanisms than those of similar tumors in adults.

Adolescent↗
PubMed1994

Isolated lumbosacral neurenteric cyst with partial sacral agenesis: case report.

A case of an isolated intraspinal lumbosacral neurenteric cyst in a 5-year-old girl with partial sacral agenesis is reported. The cyst wall contained transitional epithelium and smooth muscle characteristic of the urinary bladder, suggesting a possible cloacal origin of the cyst. No prior cases of concomitant neurenteric cysts with partial or complete sacral agenesis have been reported, and the occurrence of an isolated intradural extramedullary sacral neurenteric cyst is rare. The possible pathogenesis of this lesion is described.

Child, Preschool↗
PubMed1993

Absence of p53 mutations in childhood central nervous system primitive neuroectodermal tumors.

The primitive neuroectodermal tumor of the central nervous system is one of a number of tumors in which deletions on chromosome 17p have been identified. The tumor suppressor gene, p53, is located in the region of the deletion. To determine if the p53 gene is involved in the development of primitive neuroectodermal tumors, deoxyribonucleic acid (DNA) blot analysis, ribonucleic acid blot analysis, and p53 complementary DNA sequencing were performed on 34 primitive neuroectodermal tumors removed from children. No rearrangement in the gene was detected in 21 tumors. The p53 messenger ribonucleic acid was of the expected size in all 18 tumors for which ribonucleic acid was available. Sequencing of p53 Exons 5 through 9 revealed a mutation in the cell line DAOY and in only 1 of 14 tumors examined. A DNA rearrangement was detected in the DNA from one tumor with a probe mapping to the distal portion of 17p. Taken together, these data suggest that the p53 gene is not involved in the development of most primitive neuroectodermal tumors. In addition, a gene of interest may be present on distal 17p.

Adolescent↗
PubMed1992

Cytogenetic analysis of 39 pediatric central nervous system tumors.

Consistent cytogenetic abnormalities have been described in many pediatric solid tumors, including Ewing's sarcoma, Wilms' tumor, and neuroblastoma. Similar analysis of pediatric central nervous system (CNS) tumors has been hampered by technical problems. We report chromosome results from 39 pediatric CNS tumors. Abnormalities of chromosome 17 were noted in 3 of 11 primitive neuroectodermal tumors (including i(17q) in 2 tumors), confirming data observed by other investigators. Cells from 2 of 11 primitive neuroectodermal tumors (PNET) exhibited loss or structural abnormalities involving chromosome 11. Loss or distal deletion of chromosome 7q was noted in cells from two PNETs. Because other investigators have shown loss of heterozygosity on 17p in about one-third of PNET, we propose that chromosome regions 7q and 11 are areas worthy of further study in pediatric PNET. Numerical abnormalities were noted in 6 of 21 astrocytomas. Hyperdiploidy was demonstrated in 1 of 4 pilocytic astrocytomas and pseudopolyploidy was demonstrated in 4 of 13 anaplastic astrocytomas. Structural chromosome abnormalities (translocations, deletions) were noted in 4 of 13 anaplastic astrocytomas. Complex structural anomalies were observed in one craniopharyngioma. A rhabdoid tumor of the brain exhibited multiple complex structural rearrangements but did not exhibit the monosomy 22 observed in some rhabdoid tumors. Hypodiploidy and loss of chromosome 22 were noted in a clinically aggressive meningioma, corroborating observations by other investigators.

Astrocytoma↗
PubMed1992

Benign cerebellar astrocytomas of childhood.

Benign cerebellar astrocytomas of childhood are potentially surgically curable lesions. Histologically, these neoplasms can be divided into pilocytic and diffuse astrocytomas. Whether there is a difference in the recurrence rate between these two tumor types after a surgical resection is not clear. In addition, the role of immediate postoperative imaging in predicting a recurrence has not been established. To answer these questions, we have reviewed the charts of 23 patients with benign cerebellar astrocytomas treated at Childrens Hospital of Los Angeles over a 10-year period (1977-1987). Of the 23 tumors, 15 were pilocytic and 8 were diffuse. All patients underwent an attempted gross total surgical removal of the tumor, and all patients had a postoperative computed tomographic (CT) scan with and without intravenously administered contrast material performed within 72 hours of the operation. Based on the postoperative CT scan, 12 patients had residual tumors. Seven of the subtotally resected tumors were pilocytic (7 of 15), and 5 were diffuse (5 of 8). Interestingly, the surgeon believed that a gross total resection had been obtained in 9 of these patients. There have been 4 recurrences in these 23 patients, with a mean follow-up of 4.9 years. All recurrences were in patients with subtotal resections. Of the 11 patients with a total resection of the tumor, 7 developed a small rim of enhancement on subsequent scans an average of 5 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Management of symptomatic chronic extra-axial fluid collections in pediatric patients.

The records of 103 pediatric patients having symptomatic chronic extra-axial fluid collections treated at Children's Hospital of Los Angeles from 1977 to 1988 were reviewed. Patients were treated with observation, serial percutaneous needle drainage, drainage through burr holes, drainage into a closed external drainage system, or subdural to peritoneal shunt. If the initial treatment was not effective, additional forms of treatment were instituted. Shunts, ultimately used in 73% of the patients, proved to be the most effective treatment. Of the group with shunts, the extra-axial fluid was unilateral in 20% and bilateral in 80%. In those patients with bilateral effusions, no difference in efficacy of shunts was seen in patients treated with bilateral versus unilateral shunts. Of the 75 patients with shunts, 12% required a shunt revision for progressive or recurrent symptoms. Shunt infections occurred in 3% of the patients, necessitating removal of the shunt and treatment with antibiotics. Eosinophilia in the subdural fluid was associated with shunt obstruction requiring revision. The shunt was never removed in 51% of patients with no untoward effects. This study demonstrates that the most efficacious treatment of symptomatic chronic extra-axial fluid collections in children is a unilateral subdural to peritoneal shunt. The shunt need not be removed after resolution of the fluid collections.

Adolescent↗
PubMed1992

Development of multidrug resistance in a primitive neuroectodermal tumor cell line.

Drug resistance remains a formidable obstacle to the successful treatment of pediatric primitive neuroectodermal tumors. Resistance to chemotherapeutic agents may be related, in part, to expression of the multidrug resistance gene 1 (MDR1). The protein product of this gene, P-glycoprotein, confers resistance to multiple unrelated antineoplastic drugs. The cell line DAOY, derived from a primitive neuroectodermal tumor, was used as an in vitro model to examine the development of drug resistance. Cell lines resistant to actinomycin D were developed by the growth of DAOY in increasing concentrations of the drug. The IC50 (concentration of drug needed to induce a 50% reduction in cell growth) of the resultant lines to actinomycin D was more than 10 times that of the parental line. The resistant lines were cross-resistant to VP-16 (etoposide), despite lack of previous exposure to this drug. The resistance to actinomycin D was attenuated in the presence of verapamil, a known inhibitor of P-glycoprotein. The MDR1 gene was not expressed by the parental DAOY line at the messenger ribonucleic acid (RNA) and protein level. Expression of the MDR1 gene was documented in the resistant lines by RNA blot and immunoblot techniques. These results suggest that exposure to chemotherapeutic drugs can induce classical multidrug resistance in primitive neuroectodermal tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Multidrug resistance gene expression in pediatric primitive neuroectodermal tumors of the central nervous system.

Pediatric primitive neuroectodermal tumor (PNET) is a malignancy of the central nervous system currently treated with surgery, radiation therapy, and chemotherapy. Despite aggressive management, tumors recur in almost one-half of all patients. Drug resistance of tumor cells may, in part, explain the poor outcome. Resistance to chemotherapeutic agents may be related to expression of the multidrug resistance gene (MDR1) and its protein product, P-glycoprotein. The role of MDR1 in 16 instances of PNET was investigated using Western blot analysis to detect the expression of P-glycoprotein, messenger ribonucleic acid (mRNA), polymerase chain reaction to detect MDR1 mRNA expression, and Southern blot analysis to assess gene amplification. Analysis of proteins extracted from 15 tumors revealed that two of the 15 patients expressed detectable levels of P-glycoprotein. Polymerase chain reaction of ribonucleic acid from 12 PNET's revealed that six of the 12 patients (four of 10 de novo tumors and both recurrent tumors) expressed MDR1 mRNA. Southern blot analysis of deoxyribonucleic acid from 16 PNET's revealed no evidence of MDR1 amplification in any tumor. This is the first report of MDR1 expression in pediatric brain tumors. These data suggest a possible role for MDR1 in de novo and acquired drug resistance in PNET's.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Spinal arachnoid cysts in the pediatric age group: an association with neural tube defects.

Between 1979 and 1991, spinal arachnoid cysts were found in 11 patients aged 19 months to 18 years (mean age 5 1/2 years). Of the 11 patients, six had a myelomeningocele and one diastematomyelia. The presenting symptoms included radicular pain (one patient), progressive weakness (three), increasing scoliosis (one), worsening spasticity (three), and recurrent urinary tract infections and progressive constipation (one). Two patients showed no symptoms from the spinal arachnoid cyst. The distribution of lesions was as follows: cervicomedullary (one patient), cervical (one), cervicothoracic (two), thoracic (four), lumbar (two), and sacral (one). Four of the 11 arachnoid cysts (all intradural) were located anterior to the spinal cord, three of which were in children with a myelomeningocele. Only two of the cysts were extradural; both were found in the lumbosacral region, and one was associated with diastematomyelia. Eight patients were treated with fenestration and/or resection of the cyst wall. Three patients with anterior cysts were treated with shunts, a cyst-to-pleural space shunt in two and a cyst-to-subarachnoid space shunt in one. All of the patients either improved or exhibited an arrest in the progression of their symptoms. Spinal arachnoid cysts are a treatable cause of progressive neurological deficits and, in this series, were frequently found in patients with neural tube defects.

Adolescent↗
PubMed1992

Spinal cord compression by epidural tumors in childhood.

Epidural malignancy is the most common cause of nontraumatic spinal cord compression in children. Many different tumors may cause compression, either at presentation or sometime during treatment. Treatment options include surgery, irradiation, and chemotherapy. The decision as to the correct option depends on the tumor type and the degree of compression present.

Child↗
PubMed1992

Diffuse arteriovenous malformations: a clinical, radiological, and pathological description.

In a review of our series of patients with arteriovenous malformations (AVMs), a group with atypical angiographic and histopathological characteristics was discovered. Unlike the typical AVM, these lesions contained normal cerebral tissue between the abnormal vessels. We call these lesions diffuse AVMs, and think that this AVM represents one end of the AVM spectrum from a tight nidus to a diffuse lesion. The mean age of these patients was 18.1 years. Eight patients presented with an intracerebral hemorrhage, two with seizures, one with headache without hemorrhage, and one with ischemic symptoms compatible with vascular steal. Cerebral angiography revealed three AVMs to be 2 to 4 cm in diameter, four were 4 to 6 cm in diameter, and five were > 6 cm in diameter. Characteristic angiographic features included multiple small arterial feeders, small ectatic vessels in the malformation itself, multiple small draining veins, and a diffuse, puddling appearance of the contrast dye. Despite 16 operations in 11 patients, complete resection of the AVM was accomplished in only 8. The four patients with residual disease have received radiation therapy. Histopathology of the surgical specimens found AVM vessels interspersed among normal appearing neurons and white matter. Leptomeningeal angiodysplasia was noted when the cerebral cortex was involved. Gliosis was noted in some cases. Diffuse AVMs represent a difficult surgical challenge and recognition of the lesion aids in surgical planning.

Adolescent↗
PubMed1991

Loss of heterozygosity on 6q, 16q, and 17p in human central nervous system primitive neuroectodermal tumors.

The loss of genetic material from specific chromosomal locations in a given tumor type has been taken for evidence of the importance of tumor suppressor genes at these loci in the genesis of the tumor. The primitive neuroectodermal tumor of the central nervous system has such a loss on 17p in one-third of tumors. In this report, a detailed analysis of 17p loss in 23 tumors has been performed using 10 probes mapping to this region. In addition, an analysis for allelic deletion on chromosomes 6q, 16q, and 22q has been performed. Six of the 23 tumors showed loss of markers on 17p, and the area of common loss spanned 17p11.2 to 17pter. Five of 23 tumors showed loss of markers on 6q, and 3 showed loss on 16q. No tumor lost markers on 22q. Only one tumor showed loss at more than one location. These data suggest that primitive neuroectodermal tumors either are a heterogeneous group of tumors with more than one mechanism leading to a tumor or that more than one recessive oncogene may play a role in the genesis of these tumors.

Adult↗
PubMed1991

Treatment of spinal cord compression by epidural malignancy in childhood.

Epidural spinal cord compression by a malignant tumor is a rare occurrence in children. Both the tumors involved and the extent of involvement of the vertebral column are different in children and adults. Often, the epidural tumor in a child is identified before significant spinal canal compromise has occurred, and these children frequently can be managed by radiation therapy and/or chemotherapy. There is a group of children, however, who have severe spinal canal encroachment by a tumor, as evidenced by a near complete or complete block on myelography. In this study, we report a group of patients with severe spinal cord compression, as documented by imaging studies. We compared the results of a decompressive laminectomy and subtotal tumor resection followed by adjuvant therapy with the results obtained with radiation therapy and/or chemotherapy alone. Thirty-three patients met the criteria for inclusion in the study. Twenty-six were treated with a laminectomy and adjuvant therapy, and 7 were treated without surgical intervention. With surgical therapy, 25 of 26 epidurals were either improved or stable, whereas 4 of 7 nonsurgical patients deteriorated. Especially notable was a decrease in pain in the operative patients immediately after their procedure. There was no surgical mortality or morbidity. The results of this study indicate that children with severe spinal cord compression as evidenced by a near complete or complete block on myelography or filling of 50% or more of the spinal canal on magnetic resonance imaging are best treated by a combination of surgical decompression and tumor removal followed by adjuvant therapy.

Adolescent↗
PubMed1991

Ventricular cerebrospinal fluid eosinophilia in children with ventriculoperitoneal shunts.

To determine the significance of cerebrospinal fluid (CSF) eosinophilia, the charts of 106 patients treated with shunt-related procedures during the calendar year 1985 were reviewed. Sixty-nine patients presented for a shunt revision; their charts were retrospectively reviewed from the time of shunt insertion until January, 1988. The remaining 37 patients had a ventriculoperitoneal shunt inserted during the study period and were subsequently followed to January, 1988. A total of 558 shunt-related procedures were performed on these patients during the study period, with a mean follow-up period of 6.9 years. The infection rate was 3.8%. Eosinophilia was diagnosed when eosinophils accounted for 8% or more of the total CSF white blood cell count. Ventricular CSF eosinophilia occurred in 36 patients sometime during their clinical course. These 36 patients required a mean of 8.5 shunt revisions, while the remaining patients required a mean of 2.5 revisions (p less than 0.001). Shunt infections were also more frequent in patients with eosinophilia (p less than 0.01). In no case was peripheral eosinophilia or a parasitic infection present. This study demonstrates that CSF eosinophilia is common in children with shunts. Children with this laboratory finding will experience more shunt failures. In addition, the new appearance of eosinophilia in the CSF of a patient with a shunt in place suggests the possibility of a shunt infection.

Brain Diseases↗