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Biomedical subjects

G N Fuller

Publications and source records attributed to G N Fuller.

At least 73 records · Page 4Linked to original sources

Intracranial metastatic melanoma: correlation between MR imaging characteristics and melanin content.

OBJECTIVE: Preliminary reports based on limited numbers of cases have proposed that specific MR imaging patterns may permit a distinction between melanotic and amelanotic brain metastases in melanoma patients. The purpose of this study was to test this hypothesis by categorizing MR images obtained from a large series of patients and correlating the results with the percentage of melanin-containing cells in surgically resected metastases. SUBJECTS AND METHODS: The MR images of 30 patients with histologically proven intracerebral melanoma were reviewed retrospectively. Precontrast MR images were obtained with T1-weighted spin-echo sequences in axial and sagittal sections and with proton density-weighted and T2-weighted sequences in axial sections. After IV injection of gadopentetate dimeglumine (0.1 mmol/kg of body weight), T1-weighted images were obtained in axial and coronal sections. All patients had undergone gross total resection of the evaluated lesions. MR images of the metastases were reviewed and sorted into four groups on the basis of putative patterns: (1) melanotic pattern--hyperintense in relation to cortex on T1-weighted images, hypointense in relation to cortex on T2-weighted images, and isointense or hyperintense in relation to cortex on proton density-weighted images; (2) amelanotic pattern--hypointense or isointense in relation to cortex on T1-weighted images and hyperintense or isointense in relation to cortex on T2-weighted and proton density-weighted images; (3) indeterminate, or mixed, pattern--MR imaging characteristics that did not conform to those of one of the first two categories; and (4) hematoma pattern--MR imaging features that exhibited only hematoma characteristics. Tissue sections from all evaluated lesions were independently reviewed by a neuropathologist (G.N.F.), and the percentage of melanin-containing tumor cells in each resected metastatic lesion was estimated. The MR imaging data and histologic data were then compared to assess the predictive value of the MR imaging patterns. RESULTS: Forty-two metastatic lesions were identified and categorized by MR imaging pattern as follows: 10 melanotic, 11 indeterminate (mixed), 16 amelanotic, and five hematoma. Correlation with histologic findings revealed that a majority (7/10) of lesions that exhibited a melanotic MR imaging pattern had more than 10% melanin-containing cells, over half (9/16) of lesions that exhibited an amelanotic MR imaging pattern contained histologically identifiable melanin (but always in less than 10% of cells), and lesions that exhibited a mixed MR imaging pattern were either amelanotic or contained less than 10% melanotic cells. Conversely, a majority of lesions containing more than 10% melanotic cells (7/8) demonstrated the typical melanotic MR imaging pattern, lesions with less than 10% melanin-containing cells exhibited a variety of MR imaging patterns, and only about half of patients with amelanotic lesions (6/13) showed the characteristic amelanotic MR imaging pattern. For five lesions, potentially informative imaging data on melanin content was obscured by histologically documented hematoma formation. CONCLUSION: Only a minority of melanoma metastases have the anticipated MR imaging findings of melanotic melanoma, which consist of high signal intensity relative to that of cortex on T1-weighted images and low signal intensity relative to that of cortex on T2-weighted images. Of tumors that do exhibit this melanotic pattern, the majority have more than 10% melanin-containing cells. The putative MR imaging pattern for amelanotic melanoma is nonspecific, as over half of tumors with this pattern contain melanin.

Adult↗

Management of pineal non-germinoma germ cell tumor with residual teratoma and normal alpha-fetoprotein.

A 16-year-old white male presented with multiple abnormal extraocular movements secondary to an enhancing pineal tumor. Subtotal resection of the lesion revealed a mixed malignant germ cell tumor. The preoperative serum alpha-fetoprotein (AFP) was markedly elevated at 155 IU/L. The patient subsequently received radiotherapy and adjuvant chemotherapy consisting of cisplatin rotating monthly with vincristine and cyclophosphamide, with dramatic tumor regression and return of AFP to normal. Eighteen months later the persistence of a substantial tumor mass despite a normal AFP raised concern for residual active tumor. Histological examination of the resected lesion revealed benign teratoma and fibrous tissue. Repeat management of mixed malignant germ cell tumors, which demonstrate a persistent mass following an initial response to treatment.

Adolescent↗

Utility of postmortem magnetic resonance imaging in clinical neuropathology.

Over 200 brains were examined by postmortem magnetic resonance imaging to determine the utility of this imaging procedure as an adjunct to the standard postmortem examination of the brain and spinal cord. One unembalmed cadaver was also studied using a conventional 1.5-tesla (T) field-strength unit, and three formalin-fixed sections of the hippocampus were imaged using a high field-strength (7.0-T) prototype imaging system. The postmortem magnetic resonance images proved to be an invaluable aid that complemented the standard pathologic examination of the brain and spinal cord. The compelling advantages of this postmortem radiographic procedure included the three-dimensional aspects of the images; the ability to detect mineral (ie, iron) deposits; small focal lesions such as hemorrhages or infarcts; and the ability to evaluate the extent of cerebral edema. For the same reasons, as well as its archival potential for documenting the topographic distribution of pathologic processes, this technique has great promise for forensic cases. High field-strength (7.0-T) imaging brought the resolution of magnetic resonance to the microscopic level and reaffirmed the potential value of magnetic resonance imaging for diagnostic and investigative studies in which both the histologic and fine radiologic features of lesions are of interest.

Autopsy↗

Lactotetraose series ganglioside 3',6'-isoLD1 in tumors of central nervous and other systems in vitro and in vivo.

Two monoclonal antibodies, DMAb-21 and DMAb-22, directed against the lactotetraose series ganglioside-associated epitope IV3NeuAc,III6-NeuAcLcOse4Cer (3',6'-isoLD1), were found to define the minimum binding epitope NeuAc(or NeuGc)alpha 2-3Gal beta 1-3(NeuAc or NeuGc)alpha 2-6GlcNAc. The distribution of 3',6'-isoLD1 in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Only 4 of 26 cell lines, 3 teratomas and 1 pancreatic adenocarcinoma, expressed detectable 3',6'-isoLD1 when cultured in vitro; none of 14 tested glioma lines, including 2 that expressed the monosialo-precursor IV3NeuAcLcOse4Cer in vitro, expressed detectable levels. Expression of 3',6'-isoLD1 was more frequent when neoplastic cells were grown in xenograft form in athymic mice; 4 of 10 glioma and 2 of 2 teratoma xenograft ganglioside extracts were positive for 3',6'-isoLD1. The absence of 3',6'-isoLD1 in cultured tumor cells of the central nervous system and its proportional increased presence in tumor cells of the same origin grown in vivo further supports previous studies suggesting that ganglioside expression may be modified by environmental forces. The expression of lacto series gangliosides both in vitro and in vivo by teratoma and pancreatic adenocarcinoma cells, as opposed to only in vivo expression by glioma cells, suggests that tissue-specific forces may also exist. Immunohistochemical localization of 3',6'-isoLD1 in frozen sections of primary central nervous system neoplasms including those of glial and nonglial origin was performed; 20 of 30 (67%) of glial tumors were positive. Among nonglial tumors, 21 of 34 (62%) of epithelial cancers were reactive with anti-3',6'-isoLD1 monoclonal antibodies; notably negative were carcinomas of the ovary and lung carcinomas of all subtypes. Lymphomas and infiltrative lymphocytes were uniformly negative. The restriction of 3',6'-isoLD1 expression within the human central nervous system to periods of fetal-neonatal astroglial proliferation, to intense reactive astrocytosis, and to primary neoplasms, and the production of specific monoclonal antibodies to this epitope provide a specific complex for immunolocalization and, eventually, immunotherapy.

Animals↗

Comparison of serial PET and MRI scans in a pediatric patient with a brainstem glioma.

Profound clinical deficits may be associated with insults to the brainstem, making management of patients with brainstem gliomas very complex. Small changes in the radiographic appearance of a brainstem tumor may be associated with significant clinical deterioration. Furthermore, both magnetic resonance imaging and computed tomography are frequently unable to differentiate between therapy-related tissue reactions and progressive tumor. Two clinical scenarios particularly difficult to resolve include: (1) transient radiographic and clinical deterioration following hyperfractionated radiotherapy, and (2) clinical deterioration in a patient who has failed initial therapy, but has stable radiographic findings following a second therapy. We report a child with a pontine glioma whose tumor progression was demonstrated more convincingly with a 18F-deoxyglucose positron emission scan than with magnetic resonance imaging. PET scans may be helpful in confirming that tumor progression is responsible for clinical deterioration in a patient whose MRI scans remain stable.

Brain Neoplasms↗

Neuropathology, cell biology, and newer diagnostic methods.

Recent publications emphasized the correlation between molecular events in brain tumors and clinical outcome. Alterations in tumor-suppressor genes, growth factors, and enzyme systems have been previously described in gliomas; the relationships between these various changes and tumor grade, growth rate, and response to therapy are subjects of current investigations. Loss of genetic heterozygosity on chromosomes 10 and 17p, amplification and rearrangement of the epidermal growth factor receptor gene, express ion of its protein product, and changes in chromosomes 9, 19, and the enzyme system protein kinase C are the specific molecular events that were compared. Changes in chromosome 22 were correlated with histologic features of meningioma. Various methods of measuring tumor cell proliferation (proliferating cell nuclear antigen, bromodeoxyuridine, Ki-67, nucleolar organizer regions, and DNA flow cytometry) are being compared with each other and correlated with clinical outcome in an attempt to validate these methods and to discover the most relevant one. More recently described tumor types continue to be characterized using standard techniques and some of these newer methods. Neurocytoma has been morphologically and immunochemically defined as a neuronal neoplasm, but determination of the full compass of its clinical behavior and position in the continuum of cerebral neuronal tumors awaits additional studies.

Brain Neoplasms↗

Nature and incidence of peripheral nerve syndromes in HIV infection.

Fifty four patients with peripheral nerve syndromes were seen during a 15 month period in a population of about 1500 HIV infected patients at all stages of the disease. Distal symmetrical peripheral neuropathies were seen in 38 of the 54 patients, (11.5% of AIDS patients) and could be distinguished into two forms. The most common (n = 25) was a painful peripheral neuropathy during AIDS, which is distinct clinically and pathologically, having axonal atrophy, and is associated with cytomegalovirus infection at other sites. The 13 non-painful neuropathies seen were more heterogeneous. Lumbosacral polyradiculopathy associated with cytomegalovirus and lymphomatous mononeuritis multiplex occurred in fewer than 1% of AIDS patients. Mononeuropathies were seen in 3% of AIDS patients. No patients with acute or chronic inflammatory demyelinating polyradiculoneuropathies were seen. The annual incidence of neuropathies during the AIDS related complex stage was less than 1%; none were seen in asymptomatic HIV seropositive patients.

AIDS-Related Complex↗

Migraine madness: recurrent psychosis after migraine.

A 69 year old man with longstanding migraine with aura had four episodes of psychosis lasting 7-28 days during a 17 year period. During attacks he had formed visual hallucination and delusions, including reduplicative paramnesia. His mother was similarly affected. His EEG showed symmetrical frontal delta waves. The time course and EEG changes are similar to acute confusional migraine. The reduplicative paramnesia suggests a focal non-dominant hemisphere dysfunction.

Aged↗

Successful therapy for trilateral retinoblastoma.

Trilateral retinoblastoma, the intracranial malignancy associated with bilateral retinoblastoma, is an uncommon and clinically aggressive malignancy with a uniformly fatal outcome. Three children with newly diagnosed trilateral retinoblastoma were treated with systemic (cyclophosphamide and vincristine) and intrathecal (methotrexate, hydrocortisone, and cytarabine) chemotherapy, as well as craniospinal irradiation (one patient) in addition to therapy of the eye lesions. All three patients have had partial or complete response of the pineal tumors to chemotherapy, with no active disease eight or more years, 33 or more months, and 12 or more months, respectively, after diagnosis of the lesions.

Antineoplastic Combined Chemotherapy Protocols↗

Loss of heterozygosity for 10q loci in human gliomas.

Cytogenetic and RFLP studies have shown that chromosome 10 is frequently lost in tumor cells from glioblastomas, suggesting that a suppressor gene important in tumorigenesis is present on this chromosome. Forty-one tumors were examined for loss of heterozygosity at 23 loci on chromosome 10 to determine the smallest common deletion interval on this chromosome. Seven tumors did not lose heterozygosity for any of the markers. Twenty-three tumors lost an allele for all the informative loci. In 11 tumors heterozygosity was maintained at some loci and lost at other loci, indicating partial deletion of chromosome 10. The common region of deletion in these 11 tumors was located in 10q24-q26 between the markers pHUK-8 and pMCT122.2.

Alleles↗

Amplified cellular oncogenes in neoplasms of the human central nervous system.

Significant advances have recently been made in a number of areas concerning central nervous system (CNS) neoplasia. Particularly salient are the following: (1) gene amplification is related to increasing grade of human glioma malignancy and occurs in approximately 40% of the most common and most malignant variety of glioma, glioblastoma multiforme (GBM), (2) by far the most commonly amplified gene in glioblastomas is the epidermal growth factor receptor (EGFR) gene, which is amplified in about one third of GBMs, (3) a small percentage of GBMs amplify N-myc or the novel sequence gli, (4) the EGFR gene is rearranged in at least half of gliomas in which it is amplified, and (5) EGFR gene rearrangement results in external domain deletions that yield truncated EGF receptors. Antibodies specific for the mutant EGF receptor fusion junction have been successfully produced and provide stimulating new potential avenues for tumor imaging and therapy. For pediatric CNS neoplasms, only medulloblastoma has been investigated in adequate numbers; a small percentage exhibit amplification of either the N-myc or c-myc genes.

Adult↗