Biomedical subjects

M L Estes

Publications and source records attributed to M L Estes.

At least 19 recordsLinked to original sources

PubMed2000

Interobserver reproducibility among neuropathologists and surgical pathologists in fibrillary astrocytoma grading.

UNLABELLED: Many of the problems associated with the current grading approaches for fibrillary astrocytomas center around the lack of consistency in grading. This study compares the diagnoses of five neuropathologists with five experienced surgical pathologists with regard to assigning astrocytoma grade. Thirty neoplastic and non-neoplastic lesions were sent to each of five neuropathologists and five surgical pathologists for placement into one of three grades as outlined by modified Ringertz schema. Grading criteria (Burger et al., 1985. Cancer 56:1106-1111) were distributed to all participants, who have been practicing for at least 5 years. An additional category for non-neoplastic or normal tissue was also provided. The diagnoses, based on the majority opinion of the neuropathologist group, included six low grade astrocytomas, 11 anaplastic astrocytomas, seven glioblastoma multiforme, and six normal/reactive lesions. Agreement by all neuropathologists was reached in 12 cases (40%). A discrepant diagnosis was obtained in one of five neuropathologists in 14 additional cases (46.7%). In the remaining four cases, two neuropathologists deviated from the majority opinion; in each of these cases, the diagnostic problem involved differentiating tumor from reactive gliosis. All five surgical pathologists agreed in six cases (20%). One discrepant diagnosis among the surgical pathologist group was seen in seven cases (23.3%). In the remaining 17 cases, two or more discrepant diagnoses were obtained (56.7%); discrepancies in these cases included differences in assignment of tumor grade and in distinguishing low grade astrocytoma from gliosis. IN CONCLUSION: (1) it is likely that experience with grading accounts for the better level of agreement among the neuropathologist group (kappa statistic 0.63) versus the surgical pathologist group (kappa statistic 0.36); (2) in most cases, the neuropathologists all agreed or had one discrepant diagnosis (86.7%) versus the surgical pathologist group (43.3%); (3) the discrepancies in diagnosis among both groups is likely related, in good part, to the limitations of the grading schema in fully enumerating the spectrum of such grading parameters as cytologic atypia and vascular proliferation.

Astrocytoma↗

PubMed2000

Anti-sense oligonucleotide of p21(waf1/cip1) prevents interleukin 4-mediated elevation of p27(kip1) in low grade astrocytoma cells.

Elevation of the cyclin-dependent kinase (cdk) inhibitor, p27(kip1) is necessary for Interleukin (IL)-4-mediated growth arrest of human low grade astrocytoma (RTLGA) cells and occurs at 24 h of treatment. Pathways involved in IL4 alteration of p27(kip1) are unknown, however. Here we investigated whether other cdk inhibitors contributed to the actions of IL-4 on RTLGA cells. By 12 h of IL-4 treatment, both cdk4 and cdk2 kinase activities against the retinoblastoma protein (pRb) were reduced and nuclear entry of pRb was prohibited. Twelve-hour cdk complexes contained elevated p21(waf1/cip1) but not p27(kip1), p15(ink4B) or p16(ink4A). IL-4 increased p21(waf1/cip1) but not p27(kip1) mRNA levels, and stimulated luciferase activity of a p21(waf1/cip1) promoter-luciferase reporter. In p53-mutant WITG3 cells, IL-4 did not alter p21(waf1/cip1) mRNA and promoter-luciferase activity or p27(kipl) protein, suggesting a need for functional p53. STAT6 phosphorylation by IL-4, however, occurred in both p53-mutant WITG3 and p53-functional RTLGA cells. Pre-treatment of RTLGA with anti-sense but not missense p21(waf1/cip1) oligonucleotide prior to IL-4: (a) restored cdk activities; (b) reduced cdk4-associated p21(waf1/cip1) levels; (c) prevented p27(kipl) elevation; and (d) reversed growth arrest. These results are the first to suggest that p21(waf1/cip1) is essential for IL-4-mediated elevation of p27(kip) and growth arrest of astrocytoma cells.

Astrocytoma↗

PubMed2000

In vivo expression of the interleukin 4 receptor alpha by astrocytes in epilepsy cerebral cortex.

We reported previously that non-neoplastic astrocytes (derived from brain tissues of patients with epilepsy) expressed interleukin 4 receptor alpha (IL-4Ralpha) and responded to interleukin 4 (IL-4) in culture. To determine whether reactivity of cultured astrocytes was relevant to primary tissue, we investigated IL-4Ralpha expression in specimens of non-neoplastic cerebral cortex removed for surgical treatment of intractable epilepsy compared to specimens of glial tumours, which have been reported to contain IL-4Ralpha. Freshly frozen tissues from eight cases (four epilepsy, four malignant astrocytoma) were evaluated for IL-4Ralpha expression by reverse-transcriptase polymerase chain reaction (RT-PCR), Southern blotting, and double-labelled immunohistochemistry with antibodies to IL-4Ralpha and glial fibrillary acidic protein (GFAP). IL-4Ralpha mRNA was detectable in both non-neoplastic and neoplastic tissues, whereas interleukin 2 receptor gamma chain (IL-2Rgammac) mRNA was not found. By immunohistochemistry, IL-4Ralpha protein co-localized to cells displaying GFAP and astrocytic morphology in epilepsy tissues. As anticipated, IL-4Ralpha was detectable in astrocytoma, but, surprisingly, was also observed in GFAP-positive, non-neoplastic "reactive" astrocytes adjacent to tumour. Results are consistent with the concept that non-neoplastic epilepsy astrocytes express IL-4Ralpha in situ, thus confirming in vitro studies and implying IL-4 sensitivity in vivo.

Actins↗

PubMed2000

Interleukin-13 sensitivity and receptor phenotypes of human glial cell lines: non-neoplastic glia and low-grade astrocytoma differ from malignant glioma.

Many of the actions and receptor components of interleukin-13 (IL-13), a pleiotrophic cytokine with immunotherapeutic potential, are shared with IL-4. Because human low-grade astrocytoma cells express IL-4 receptors and their growth is arrested by IL-4, we speculated that IL-13 sensitivity and receptor expression might also be present. The purpose of the current study was to investigate IL-13 receptor components and sensitivity in a series of glial cell lines derived from adult human non-neoplastic cerebral cortex, low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Unlike peripheral blood lymphocytes (PBL), glial cells did not express IL-2 receptor gamma chain. IL-13 receptor alpha-1 (IL-13Ralpha1), however, was present in 11/13 glial lines and PBL. Deficient cell lines were all glioblastoma-derived. All anaplastic astrocytoma and glioblastoma but not other glial lines or PBL expressed IL-13 receptor alpha-2 (IL-13Ralpha2). In non-neoplastic glia, low-grade, and anaplastic astrocytoma, IL-13 decreased DNA synthesis, an effect reversible with antibody to IL-4Ralpha. Results indicate that low-grade astrocytoma cells resemble non-neoplastic glia in terms of IL-13 sensitivity and IL-4Ralpha/IL-13Ralpha1 receptor profile but alterations occur with malignant progression. Glioblastoma cells were uniformly insensitive to IL-13 and, unlike other glia, failed to phosphorylate STAT6 after IL-13 challenge. Data suggest that IL-13 and analysis of IL-13 receptors may have clinical application in glial tumors.

Astrocytoma↗

PubMed1999

Extracerebellar primitive neuroectodermal tumors: A clinicopathologic study with bcl-2 and CD99 immunohistochemistry.

Supratentorial primitive neuroectodermal tumors (S-PNETs) are uncommon lesions that occur predominantly in children and are histologically identical to cerebellar medulloblastomas. Like their cerebellar counterparts, S-PNETs often show divergent differentiation along neuronal, glial, and mesenchymal lines. The relationship of S-PNETs to medulloblastoma and other embryonal neoplasms remains controversial, largely because the cell of origin and histogenesis of these lesions are incompletely understood. To clarify these issues, we examined eight S-PNETs with antibodies to bcl-2 (an antiapoptosis protooncogene that has been postulated to be a marker of neuronal differentiation) and CD99 (a glycoprotein present in most peripheral embryonal tumors). S-PNETs in eight patients (seven males and one female; age range, 2 months to 40 years) were studied. All lesions were composed predominantly of small round cells with deeply basophilic nuclei and minimal surrounding cytoplasm. Tumors in two patients demonstrated no evidence of differentiation, two tumors neuronal differentiation only, and four tumors both neuronal and glial differentiation. No tumors stained with CD99. Three tumors showed focal, strong cytoplasmic staining with bcl-2. The positive lesions included one tumor showing neuronal differentiation only and two tumors with both neuronal and astrocytic differentiation. Patients were treated with various combinations of radiation and chemotherapy; five patients died from their tumor a mean of 1.7 years after diagnosis, two patients were alive with residual disease at 3 months and 3 years, and one patient was alive without disease at 17 months. Our findings suggest that bcl-2 positivity may identify a subgroup of patients having inhibition of apoptosis as a pathogenetic mechanism; we were unable to show any definite relationship between bcl-2 staining and neuronal differentiation. Despite their morphologic similarity, supratentorial and peripheral embryonal tumors appear to be distinct pathogenetic lesions, as evidenced by their different staining patterns with CD99.

12E7 Antigen↗

PubMed1998

Ganglioglioma and intractable epilepsy: clinical and neurophysiologic features and predictors of outcome after surgery.

PURPOSE: To review the clinical, neurophysiologic, and radiological data of patients with ganglioglioma who had undergone evaluation and surgery in our Epilepsy Program. METHODS: The medical and neurophysiologic records of 38 patients with intractable epilepsy and ganglioglioma were reviewed. Data underwent statistical analysis. RESULTS: There were 28 temporal and 10 extratemporal resections, with a mean age at seizure onset of 10.5 years and mean age at surgery of 22 years. Five tumor resections performed earlier were recorded. Twenty-nine patients had auras and 20 had secondarily generalized seizures. All 28 patients with temporal tumor had complex partial seizures. Preoperative MRI demonstrated the tumor in 36 of 36 patients: 17 of 29 demonstrated gadolinium enhancement, and 17 of 36 had mass effect. Scalp interictal sharp waves were present in 32 patients, and in 15 they were multiregional. In two patients, scalp EEG seizure onset was from the hemisphere contralateral to the tumor. Postoperatively, 79% of patients (30 of 38) were seizure-free (Engel's class I) at 6 months, 72% at 1 year (26 of 36), and 63% at 2 years (20 of 32). Excellent outcome was associated with a lower age at operation (p = 0.008), shorter duration of epilepsy (p = <0.01), absence of generalized seizures (p = <0.01), and no epileptiform discharges on a postoperative EEG (p = 0.01). CONCLUSIONS: Good surgical outcome is expected in patients with ganglioglioma despite years of medically resistant seizures. Good outcome may be achieved despite EEG findings that may conflict with tumor location, and is more likely when surgery is performed relatively soon after epilepsy onset.

Adult↗

PubMed1997

The CDK inhibitor, p27Kip1, is required for IL-4 regulation of astrocyte proliferation.

IL-4 is a pleiotrophic cytokine that has been shown to affect cells of the central nervous system. We have demonstrated that IL-4 inhibits DNA synthesis and proliferation in human astroglia expressing IL-4 receptors. In this study, we sought to identify mechanisms that could account for the antimitogenic effects of IL-4. Epidermal growth factor (EGF)-stimulated human astroglia were arrested in G1 phase by IL-4, even though IL-4 stimulated levels of the G1 cyclins, D1 and E. Histone H1 kinase activity of cdk2 immunoprecipitates, however, was sharply reduced by IL-4; impairment of kinase activity was also evident in cyclin E immunoprecipitates, which contained evidence of hypophosphorylated (inactive) cdk2 product. Reduced cyclin E-associated cdk2 activity was not due to impaired cyclin-dependent kinase-activating kinase (CAK) activity, which was unaffected by IL-4. Inactive cyclin E/cdk2 complexes from IL-4 + EGF-treated cells contained, however, strikingly elevated p27Kip1 cdk inhibitor. Elevated p27 was also detectable in whole cell lysates after 24 and 48 h of IL-4 treatment; by 72 h, p27 was no longer elevated. Pretreatment with antisense but not mismatch p27 oligonucleotides attenuated the inhibitory effects of IL-4 on DNA synthesis and histone kinase activity of cyclin E/cdk2 complexes. Antisense p27 also abrogated IL-4-mediated elevation of p27 in whole cell lysates and cyclin E/cdk2 complexes. These findings demonstrate that IL-4 regulates the cell cycle machinery of astroglial cells via a p27Kip1 braking mechanism.

Antigens, CD↗

PubMed1997

Transition to capitation. Core competencies for physician practice success.

The growth of managed care--with the resulting consolidation, cost control, and profit-oriented players entering the market--is a major source of concern. Largely due to this market evolution, physicians find themselves in the position of working within a single management paradigm and attempting to apply it in two different contexts: capitated payment systems and traditional fee-for-service medicine. This article identifies, compares, and contrasts the competencies necessary for successful practice in a managed care, as opposed to a fee-for-service, environment.

Attitude of Health Personnel↗

PubMed1997

Adult-onset nemaline myopathy: a case report and review of the literature.

Nemaline (rod) myopathy is a congenital muscle disease with a wide spectrum of phenotypes, ranging from forms with neonatal onset and fatal outcome to asymptomatic forms. An adult-onset variant is characterized by large numbers of rod-containing myofibers, numerous rods per affected myofiber, and the absence of specific structural abnormalities typical of other muscle diseases. Few cases fulfilling these criteria have been described in the literature. Rare cases have had an associated inflammatory component, and the majority of these have occurred in patients with an underlying immunologic disorder. We present an unusual case of an immunologically competent 65-year-old man with late-onset nemaline myopathy, who was previously diagnosed with an inflammatory myopathy based on a muscle biopsy that contained chronic inflammation. His symptoms consisted of a 2-year history of progressive proximal muscle weakness; his family history was unremarkable. A neurologic examination confirmed the presence of bilateral proximal muscle weakness, normal sensation, and decreased upper and lower extremity reflexes. Creatine kinase levels were normal, and electromyographic findings indicated a myopathic process. A modified trichrome stain of the right biceps muscle revealed granular, basophilic, centrally located rods in the atrophic myofibers. Ultrastructurally, these myofibers contained osmiophilic rectangular structures with a latticelike appearance typical of nemaline myopathy. This case illustrates that adult-onset nemaline myopathy, although rare, should be considered in the differential diagnosis of an inflammatory myopathy.

Age Factors↗

PubMed1996

Leukocyte adhesion molecules and x-ray energy dispersive spectroscopy in Sturge-Weber disease.

We examined the light microscopic and ultrastructural features associated with Sturge-Weber disease, including x-ray energy dispersive spectroscopy to evaluate the chemical composition of the mineralized deposits and immunofluorescence microscopy with leukocyte adhesion molecules to examine the blood vessel proliferation further. Two patients (a 17-year-old girl and a 9-month-old boy) with Sturge-Weber disease comprise this series. Mineralized deposits stained strongly positive with von Kossa and negative with Prussian blue. Transmission electron microscopy of tissue removed during a functional hemispherectomy procedure in both cases indicated that most concretions were adjacent to or in the basal lamina of parenchymal vessels; no deposits were observed in leptomeningeal vessels. Energy dispersive spectroscopy of the deposits showed emission peaks corresponding predominantly to calcium, with lesser amounts of phosphorus. Fluorescent monoclonal antibodies to leukocyte adhesion molecules (endothelial cell, vascular cell, and intercellular: ELAM-1, VCAM-1, and ICAM-1) demonstrated strong positive staining of the meningeal vessels with all three antibodies. Cortical vessels were positive only for ICAM-1. Findings based on routine staining and energy dispersive spectroscopy indicate that the mineralized deposits detected in Sturge-Weber disease are composed primarily of calcium phosphate and are located primarily in and adjacent to the vascular basal lamina. There is an aberrant expression of ELAM-1 and VCAM-1 in the meningeal vascular proliferation similar to what is observed with other vascular malformations and tumors. Parenchymal vessel changes may be secondary to the meningeal vascular proliferation.

Adolescent↗

PubMed1996

MIB1 and p53 immunoreactivity in protoplasmic astrocytomas.

Pure protoplasmic astrocytomas are a group of rarely encountered low grade astrocytic neoplasms. Relatively few studies have specifically examined this subset of tumors. A series of 18 protoplasmic astrocytomas in 14 males and four females (age range 2.5-52, mean 22 years) were studied in order to examine MIB1 (a marker of cell proliferation) and p53 (a tumor suppressor gene) immunoreactivity. All patients presented with seizures (mean duration 94 months) and three with headaches also. Eight tumors were located in the temporal lobe and six in the frontal lobe. All tumors were characterized by a proliferation of astrocytes with round nuclear contours arranged against a microcystic background. Only rare foci of mild vascular proliferation (3 tumors), rare mitotic figures (1 tumor), and mild nuclear atypia (3 tumors) were observed. Most tumors were primarily cortical in location. Necrosis was not seen in any of the tumors. MIB1 indices (number of MIB1 positive tumor cells/1000 tumor cells evaluated x 100) ranged from 0 to 4.3 (mean 0.7); in five tumors, no MIB1 staining was observed. p53 immunoreactivity was noted in 5 of 18 tumors (28%). Five patients received adjuvant radiation therapy and one adjuvant chemotherapy. At last known follow-up, 11 patients are alive with no evidence of residual tumor (mean 70 months), six patients are alive with evidence of residual tumor (mean 58 months), and one patient died of complications unrelated to the tumor (36 months) postoperatively. Based on these findings, the conclusions presented are as follows: (i) MIB1 indices are generally low in these tumors, corroborating the clinical impression of a slow growing neoplasm; and (ii) p53 immunoreactivity is observed in a minority of protoplasmic astrocytomas.

Adolescent↗

PubMed1996

In situ hybridization analysis of glial fibrillary acidic protein mRNA reveals evidence of biphasic astrocyte activation during acute experimental autoimmune encephalomyelitis.

Reactive astrogliosis is a prominent pathological feature of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. It is characterized by hypertrophy of astrocytes with increased content of glial fibrillary acidic protein (GFAP.) Studies of reactive astrocytes in acute experimental autoimmune encephalomyelitis have been complicated by the observation that the diffuse increase in GFAP immunohistochemical staining at the onset of central nervous system inflammation does not parallel the gradual increase in GFAP content probably because tissue edema enhances GFAP immunostaining. To characterize changes in GFAP expression, we performed in situ hybridization at 3- to 7-day intervals during the course of acute murine experimental autoimmune encephalomyelitis. We found a biphasic course of GFAP expression: an early phase of astrocyte reaction surrounding perivascular inflammatory cuffs and submeningeal infiltrates at the onset of central nervous system inflammation and clinical disease and a later phase of increased GFAP mRNA expression in regions of demyelination during resolution of inflammation and clinical improvement. IP-10, a member of a family of proinflammatory chemoattractant cytokines called chemokines, was expressed by astrocytes in a similar distribution as those expressing increased GFAP mRNA in the early phase of inflammation but was no detected in astrocytes in the later phase of activation. These results indicate that location and function of reactive astrocytes may vary during the course of immune-mediated demyelination.

Acute Disease↗

PubMed1995

Inhibitory effects of tamoxifen and tumor necrosis factor alpha on human glioblastoma cells.

We reported previously that tumor necrosis factor alpha (TNF alpha) inhibited proliferation and invasiveness of human malignant glial cells. Because tamoxifen, an estrogen antagonist, has also been shown to inhibit growth of such cells, we hypothesized that a combination of tamoxifen and TNF alpha might be more effective than either reagent alone. TNF alpha (1-100 ng/ml) or tamoxifen (80 ng/ml-2 micrograms/ml) alone inhibited proliferation of a human glioblastoma cell line (WITG3) in a dose-dependent fashion; in combination, tamoxifen and TNF alpha yielded additive growth inhibition. Apoptotic cells characterized by nuclear fragmentation were detectable after 48 h of TNF alpha or tamoxifen exposure and were significantly increased by combination treatment. In non-neoplastic human astroglia and fibroblasts, proliferation was unaffected by tamoxifen, and enhanced by TNF alpha as previously reported. Staurosporine (2-50 nM), which has been reported to augment the effects of TNF alpha, was less effective than tamoxifen against WITG3 and, in addition, was markedly inhibitory to non-neoplastic glial cells. Binding studies yielded no evidence of WITG3 estrogen or progesterone receptors, nor of tamoxifen effects on TNF alpha receptors. Data suggest that TNF alpha and tamoxifen in combination display growth-regulatory properties, which (a) are more inhibitory to human glioblastoma cells than either agent alone, (b) do not affect non-neoplastic glia, (c) do not require either estrogen/progesterone receptors or alteration of external TNF alpha receptors, and (d) may involve apoptosis.

Alkaloids↗

PubMed1995

Cortical dysplasia: a histopathologic study of 52 cases of partial lobectomy in patients with epilepsy.

In utero migrational abnormalities account for most cases of cortical dysplasia. The histopathologic appearance of cortical dysplasia is often varied, making recognition and classification difficult. We studied 52 patients with cortical dysplasia who underwent partial lobectomy for medically intractable seizures in order to devise a simple histopathologic classification schema. The incidence of observed dysplasia in lobectomy specimens over an 11-year period (n = 360) was 14%. Patients ranged in age from 3 months to 47 years at the time of surgery (mean, 19 years; 29 male and 23 female patients). The temporal lobe was involved in 34 patients, frontal lobe in 18, parietal lobe in four, and occipital lobe in three. In three patients multiple lobes showed dysplasia. Dysplasia was right-sided in 29 patients and left-sided in 23 patients. Dysplasia was focal in 23 patients, multifocal in four patients, and diffuse in 25 patients. Three main histologic patterns of cortical dysplasia were observed: (1) a cortical laminar architectural disorganization and/or malalignment of neurons (26 patients), (2) clusters of atypical neurons and glia within the cortex (28 patients), and (3) a hypercellular molecular layer with increased numbers of neurons and glia (31 patients). In 23 patients more than one pattern of dysplasia was identified. Coexistent tumors were present in 13 patients, including ganglioglioma (eight patients), dysembryoplastic neuroepithelial tumor (three patients), and low-grade astrocytoma (two patients). Tuberous sclerosis was present in four patients. We conclude that most types of cortical dysplasia can be divided into three main histologic patterns, facilitating the recognition of dysplasia. In addition to the known association with tuberous sclerosis, tumors may coexist with cortical dysplasia.

Adolescent↗

PubMed1995

Human astrocyte growth regulation: interleukin-4 sensitivity and receptor expression.

We previously reported that interleukin-4 (IL-4) inhibited proliferation of a human astrocytic cell line derived from non-neoplastic adult cortex. To determine whether this effect was receptor-associated and/or limited to only non-neoplastic astrocytes, we examined IL-4 responsiveness and receptor expression in human astrocytic cell lines derived from three different sources: non-neoplastic cerebral cortex (lines P1N, P2N, W3N); neoplastic low grade astrocytoma (LGA) (lines FRLGA, RTLGA); and highly malignant glioblastoma multiforme (GBM) (lines STTG1, CRTG2, WITG3, RUTG4). All lines except RUTG4 GBM expressed IL-4 receptor mRNA. Proliferation and DNA synthesis were markedly suppressed by IL-4 in a dose- and time-dependent manner in all non-neoplastic astrocyte and LGA lines, but not (0/4) GBM. This negative growth-regulatory effect of IL-4 was blocked by specific antibody to human IL-4 receptor but not by irrelevant IgG. In contrast, IL-4 stimulated interleukin-6 (IL-6) secretion in non-neoplastic astrocytes and LGA as well as in GBM cells expressing IL-4 receptor; secretion was undetectable in RUTG4 GBM which did not express receptor. These results indicate that: (i) responsiveness to IL-4 occurs in both non-neoplastic and neoplastic human astroglia; (ii) responsiveness is associated with IL-4 receptor expression; and (iii) sensitivity to negative growth signalling by IL-4 occurs selectively in astrocytes from non-neoplastic cortex or low grade neoplasia but not from highly malignant GBM.

Astrocytes↗

PubMed1995

Expression of basement membrane and endothelial cell adhesion molecules in vascular malformations of the brain: preliminary observations and working hypothesis.

Little is known about the pathogenesis and subsequent cellular biologic behaviour of human cerebral vascular malformations. Innovative therapeutic strategies will depend on more fundamental understanding of structural and functional lesion biology. We have freeze-processed four specimens of arteriovenous malformation (AVM), two cavernous malformations (CM), and resected cortex from one case of Sturge-Weber disease (SWD) for immunohistochemical studies. Probes of vascular maturity and cellular adhesion were examined, including Factor 8 related antigen (F8RAG), laminin, fibronectin, and adhesion molecules VCAM, ELAM and ICAM-1 (CD 54). Sections of the same lesions were permanently fixed and stained using Haematoxylin and Eosin, and MOVAT Pentachrome stain for identification of vascular wall structures. A double antibody staining battery was utilized with ultraviolet fluorescent microscopy, and was analysed by an observer blinded to the antibody and lesion type. All malformations showed strong expression on their luminal endothelial surface for F8RAG. There was no expression of ELAM in any lesion. Two AVMs expressed VCAM on the endothelial surface of some vessels. ICAM-1 was expressed faintly within two AVMs. The CMs expressed fibronectin within the endothelium and subendothelial matrix, and both lesions were devoid of laminin expression. The AVMs and the SWD vessels stained for laminin, while none of the AVMs expressed fibronectin. These preliminary observations are consistent with the hypothesis that AVMs and SWD represent more mature vessels, consistent with possible lesion genesis during early phases of embryonic vascular development (dysvasculogenesis). In contrast, CMs represent immature vessels devoid of laminin and other features of mature vessels, consistent with ongoing dysangiogenesis within a fibronectin rich matrix. Further studies should be aimed at better elucidation of these biologic probes, and correlation with specific lesion behaviour.

Basement Membrane↗

PubMed1995

Protoplasmic astrocytoma. A clinicopathologic study of 16 tumors.

UNLABELLED: Protoplasmic astrocytomas, composed of process-poor astrocytic cells and a microcystic background, are rare variants of low grade astrocytoma. Three hundred eight low grade astrocytomas over a 23-year period were reviewed. Sixteen (5.2%) were classified as pure protoplasmic astrocytoma. Patients (12 males, 4 females) ranged in age from 2.5 to 41 years (mean, 20.7 years). All patients presented with seizures and three had headaches. Duration of symptoms ranged from 7 months to 28 years (mean, 6.6 years). Nine tumors (56%) were left-sided and seven right-sided (44%). Seven (44%) occurred in the temporal lobe, six (37%) in the frontal lobe, two (13%) in the parietal lobe, and one (6%) in the thalamus. Surgery consisted of partial lobectomy with total tumor resection in nine and biopsy alone in seven. Five patients received adjuvant therapy with no apparent effect on survival. At frozen section, protoplasmic astrocytoma was most confused with fibrillary low grade astrocytoma (n = 6). Follow-up revealed 10 patients with no evidence of disease 2 to 108 months postoperatively (mean, 41 months), 5 patients were alive with disease 10 to 84 months postoperatively (mean, 56 months) and 1 patient died with disease at 36 months. Of patients with total tumor resection, eight had no evidence of disease and one died with disease. IN CONCLUSION: (1) protoplasmic astrocytomas in this study were more frequently observed in males at a younger mean age than fibrillary low grade astrocytomas as reported in literature; (2) temporal and frontal lobes were the most likely site of origin; and (3) complete excision may be beneficial, whereas adjuvant therapy appeared to have no effect on outcome.

Adolescent↗

PubMed1995

Childhood ganglioglioma and medically intractable epilepsy. A clinicopathological study of 15 patients and a review of the literature.

Gangliogliomas are an increasingly recognized cause of epilepsy in children. Several studies have shown that early surgical treatment is beneficial, but controversy exists regarding the type of surgical treatment required for optimal seizure control and to prevent tumor recurrence. To address this issue, we performed a retrospective review of 15 children operated on at the Cleveland Clinic during a 7-year period with medically intractable epilepsy who were found to harbor a ganglioglioma during the course of their work-up. Nine patients with mostly nondominant hemisphere tumors underwent tumor resection without the use of electrocorticography to guide additional resection of epileptogenic foci, while 6 other patients with dominant hemisphere tumors had subdural electrode grids placed to extraoperatively map zones of ictal onset and eloquent areas. The extent of tumor resection was then correlated to seizure outcome and tumor recurrence. Of the 11 patients who received a gross total resection, 9 are seizure-free while 2 have a greater than 90% reduction in their seizure frequency (100% 'good' outcome). There was no tumor recurrence in this group. Of the 4 patients who underwent a subtotal tumor resection, 1 is seizure-free while 3 have persistent seizures (25% 'good' outcome). All patients in this group have stable disease on follow-up magnetic resonance imaging. In those patients who received subdural electrode grids, the extent of resection of the zones of ictal onset did not correlate with seizure outcome. The mean follow-up was 42 months. We conclude that complete tumor resection is the most important factor for optimal seizure control and to prevent tumor recurrence.

Adolescent↗