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Biomedical subjects

D N Louis

Publications and source records attributed to D N Louis.

At least 163 records · Page 9Linked to original sources

Intramedullary cavernous angiomas of the spinal cord: clinical presentation, pathological features, and surgical management.

Cavernous angiomas of the spinal cord are rare lesions that can cause severe neurological symptoms. We add a series of 6 patients with intramedullary cavernous angiomas of the spinal cord to 30 patients with 31 histologically verified lesions already described in the literature. Four types of clinical presentation were seen in the 36 patients: 1) discrete episodes of neurological deterioration with varying degrees of recovery between episodes (13 patients); 2) slow progression of neurological decline (12 patients); 3) acute onset of symptoms with rapid decline (8 patients); and 4) acute onset of mild symptoms with subsequent gradual decline lasting weeks to months (3 patients). Of the 36 patients, 25 (69%) were women and 11 (31%) were men. The peak age of presentation was in the fourth decade. The thoracic spinal cord was affected in more than half the patients, with the cervical cord being the next most common location. Histological examination demonstrated the closely apposed vascular channels characteristic of cavernous angiomas. While most vascular channels were thickened and hyalinized, three angiomas had foci of small vessels resembling a capillary angioma. The available data suggest that surgical management of intramedullary angiomas should attempt complete extirpation. The lesions are often well circumscribed with a glial plane between the lesion and normal cord. However, spinal cord angiomas, unlike cranial lesions, have little room for enlargement before devastating symptoms occur. We achieved complete excision in all of our patients, who are all ambulatory and have improved symptoms. Little, if any, increase in neurological deficit was caused by myelotomy and lesion excision. These spinal lesions should be considered for surgery early, before repeated hemorrhage or enlargement can occur.

Cross-Sectional Studies↗

The treatment of oligodendrogliomas and mixed oligodendroglioma-astrocytomas with PCV chemotherapy.

Malignant oligodendrogliomas have been shown to be responsive to chemotherapy. The authors administered systemic chemotherapy to seven patients with oligodendroglioma or anaplastic oligodendroglioma, and to 14 with mixed oligodendroglioma-astrocytoma. Fourteen patients underwent chemotherapy before and seven after irradiation. The PCV (procarbazine, methyl-1-(2-chloroethyl)-1-nitrosourea (CCNU), and vincristine) chemotherapy was administered every 6 weeks (42-day cycles) for two to five cycles as follows: CCNU, 110 mg/sq m on Day 1; procarbazine, 60 mg/sq m/day on Days 8 to 21; and vincristine, 1.4 mg/sq m/day on Days 8 and 29. Complete or partial (greater than 50% reduction in tumor mass) responses at 20 to 100+ weeks after treatment were noted in 11 (79%) of the 14 patients treated before irradiation, including two with anaplastic oligodendroglioma and nine with mixed tumors. Complete responses were seen in two patients, one with anaplastic oligodendroglioma and one with a mixed tumor. Partial responses were seen in three of seven patients treated after radiotherapy. Stabilization of tumor growth followed PCV chemotherapy in four patients (two treated before and two after radiotherapy). Tumor growth progressed in two patients during therapy despite an initial response and in two patients despite therapy. The authors conclude that mixed oligodendroglial tumors as well as anaplastic oligodendrogliomas are responsive to PCV chemotherapy.

Adult↗

Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme.

Although the loss of tumor suppressor genes and the activation of oncogenes have been established as two of the fundamental mechanisms of tumorigenesis in human cancer, little is known about the possible interactions between these two mechanisms. Loss of genetic material on chromosome 10 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequently reported genetic abnormalities in glioblastoma multiforme. In order to examine a possible correlation between these two genetic aberrations, the authors studied 106 gliomas (58 glioblastomas, 14 anaplastic astrocytomas, five astrocytomas, nine pilocytic astrocytomas, seven mixed gliomas, six oligodendrogliomas, two ependymomas, one subependymoma, one subependymal giant-cell astrocytoma, and three gangliogliomas) with Southern blot analysis for loss of heterozygosity on both arms of chromosome 10 and for amplification of the EGFR gene. Both the loss of genetic material on chromosome 10 and EGFR gene amplification were restricted to the glioblastomas. Of the 58 glioblastoma patients, 72% showed loss of chromosome 10 and 38% showed EGFR gene amplification. The remaining 28% had neither loss of chromosome 10 nor EGFR gene amplification. Without exception, the glioblastomas that exhibited EGFR gene amplification had also lost genetic material on chromosome 10 (p less than 0.001). This invariable association suggests a relationship between the two genetic events. Moreover, the presence of 15 cases of glioblastoma with loss of chromosome 10 but without EGFR gene amplification may further imply that the loss of a tumor suppressor gene (or genes) on chromosome 10 precedes EGFR gene amplification in glioblastoma tumorigenesis.

Biomarkers, Tumor↗

A (CA)n dinucleotide repeat assay for evaluating loss of allelic heterozygosity in small and archival human brain tumor specimens.

Southern blotting is a widely used method of determining loss of chromosomal alleles in tumors, but cannot be used to analyze small biopsies and most fixed, embedded tissues. These problems preclude analysis of many surgical neuropathology specimens. We have employed a polymerase chain reaction assay for loss of heterozygosity (LOH) based on the (CA)n dinucleotide repeat polymorphisms found in abundance throughout the human genome. We compared this method to conventional Southern blotting in detecting LOH on chromosome 10 in gliomas. From tissue sections of 14 paraffin-embedded, formalin-fixed gliomas, we amplified the (CA)n repeat D10S89 locus and compared (CA)n repeat patterns between tumor DNA and constitutional DNA. Loss of one chromosome 10 (CA)n repeat allele was seen in informative glioblastomas that showed allelic loss by Southern blotting, but not in gliomas that had maintained both alleles. The (CA)n repeat method can be applied to small and fixed, embedded specimens, is rapid and simple to perform, and uses highly polymorphic probes. We suggest that (CA)n repeats are a less exclusive and more rapid means of studying LOH in brain tumors than Southern blotting, and will provide further mapping data for the identification of tumor suppressor genes integral to glial tumorigenesis.

Adenine↗

Clinicopathologic correlation in a case of pupillary dilation from cerebral hemorrhage.

A patient who developed pupillary dilation on the side of a large cerebral hemorrhage underwent serial examinations, computed tomography, and magnetic resonance imaging. Autopsy dissection was performed to allow in situ examination of the structures near the third nerves and tentorial edge. The origin of the oculomotor nerve was displaced medially, causing the distal nerve to "kink" over the clivus just posterior to the clinoid. Transtentorial herniation of the medial temporal lobe did not appear to play a role in third-nerve compression.

Aged↗

Proliferating cell nuclear antigen and Ki-67 immunohistochemistry in brain tumors: a comparative study.

Proliferating cell nuclear antigen (PCNA) is a 36-kDa DNA polymerase-delta auxiliary protein which accumulates in the nucleus during S phase of the cell cycle. Immunohistochemical labeling indices (LI) of PCNA and Ki-67 were compared using an avidin-biotin complex method on frozen sections of 27 nervous system tumors. 3 normal cerebral cortices, and 3 peripheral nerves. In glial tumors, PCNA and Ki-67 LI increased with increasing tumor grade (Daumas-Duport system). In 5 low-grade glial tumors, PCNA and Ki-67 LI were less than or equal to 1%, except for one optic nerve glioma (Ki-67 LI = 6%). In 7 grade 3 astrocytomas and 1 mixed glioma, PCNA LI were less than or equal to 1-1.5%, while Ki-67 LI were 2%-10%. In 7 grade 4 astrocytomas and 1 metastatic carcinoma, PCNA LI ranged from 6%-15% while Ki-67 LI ranged from 17%-30%. In 5 of 6 schwannomas, focally high PCNA LI (4%-65%) were noted, despite low LI with Ki-67 (less than or equal to 1.6%). Scattered normal schwann cell nuclei also stained with PCNA, but normal cerebral cortex did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗

Pseudopsammomatous meningioma with elevated serum carcinoembryonic antigen: a true secretory meningioma. Case report.

A sphenoid-wing meningioma in a 60-year-old woman was accompanied by elevated serum carcinoembryonic antigen (CEA) levels, which returned to normal after removal of the tumor. Light microscopic examination revealed a secretory meningioma containing numerous pseudopsammoma bodies and a prominent vascular pattern. Immunohistochemical analysis showed the tumor cells and pseudopsammoma bodies to be CEA-positive. This case illustrates the possibility that secretory meningioma may be associated with clinically detectable secretion of CEA. The report also documents the rare occurrence of elevated serum CEA in a primary benign intracranial tumor.

Carcinoembryonic Antigen↗

Metastatic ependymoma of the sacrum.

Ependymomas originating in the sacrum or extraspinal parasacral soft tissues are rare tumors. The majority are of the myxopapillary type and may be locally destructive. Even though metastases are not uncommon in retrosacral ependymomas, they have been rarely described in intrasacral locations. A case is reported of a large intrasacral ependymoma with metastases to several vertebrae. Radiologic and pathologic studies are presented. Treatment options are discussed.

Aged↗

Central nervous system neurocytoma and neuroblastoma in adults--report of eight cases.

The clinical features, pathologic findings and treatment courses of eight adults with central nervous system small-cell neuronal tumors were reviewed. Five patients had central neurocytomas, two patients central nervous system neuroblastomas, and one patient a neurocytoma-like spinal cord tumor. The neurocytomas were intraventricular, moderately cellular tumors with bland nuclei and perinuclear halos. Patients with neurocytoma were treated with surgery, radiation therapy, and/or chemotherapy, and have followed favorable clinical courses. The neuroblastomas were intraparenchymal, hypercellular tumors with necrosis and frequent mitoses. Patients with neuroblastomas were treated with surgery, radiation therapy and chemotherapy, with some clinical response, but overall poor survival. One of the two patients developed extracranial metastasis. The spinal cord tumor had histologic features of neurocytoma, and responded well to biopsy and radiation therapy. The cases are compared with the varieties of small-celled neuronal tumors described in the literature, and pathologic, histogenetic and treatment implications are discussed.

Adult↗

A new 1.9-mu wavelength laser for neurosurgery.

The 1.9-mu wavelength component of a 1.9/1.06-mu two-wavelength laser with near-continuous wave properties was tested for its potential use in neurosurgery. The 1.9-mu wavelength has tissue-ablative capabilities, while the 1.06-mu wavelength (Nd:YAG) is suitable for achieving hemostasis. The advantages of the 1.9-mu wavelength over the CO2 laser include its ability to transmit through silica fiberoptic delivery systems and its deeper penetration in water (approximately 100 mu, a depth 10 times greater than for the CO2 laser), which is compatible with irrigation during ablation. To test the effectiveness of the laser, bilateral craniotomies were performed in anesthetized rats immobilized in a stereotactic frame. Under an operating microscope, lesions were made on the cortex by delivering the 1.9-mu laser beam through a 400-mu fiber at an average power of 1 W over a range of fluences. Subjective intraoperative observations were notable for minimal bleeding, absence of charring when the tissue was irrigated with a thin stream of saline, and uniform lesion formation. For comparison, lesions were generated with a commercially available continuous-wave CO2 laser at equivalent power and fluences. Histological specimens were divided into three groups based on the study after laser application: acute (30 minutes), subacute (48 hours), and chronic (14 days). The extent of thermal injury for the 1.9-mu laser in the acute lesions was quantitatively and histologically similar to that generated by the CO2 laser. Regions of injury extended approximately from the apex of the lesion, and crater depths generated by both lasers were similar (250 to 750 mu) in the range of fluences investigated (1.25 to 10 kJ/sq cm). Subacute and chronic histological specimens demonstrated inflammatory and repair responses that correlated with the acute injury regions in both the 1.9-mu and CO2 laser-treated specimens. This study demonstrates a neurosurgical potential for a new two-wavelength laser that ablates tissue effectively with limited thermal injury. The 1.9-mu laser is comparable to the widely used CO2 laser but offers several unique advantages, including the ability for delivery through a fiberoptic system and to irrigate tissue during use.

Animals↗

Sarcomatous proliferation of the vasculature in a subependymoma.

A case of a recurrent posterior fossa subependymoma in a 60-year-old man is reported. In the recurrent tumor, the vasculature had undergone apparent sarcomatous proliferation of the endothelial cells. The bizarre cells expanded and replaced the vessel walls, and stained for Factor VIII-related antigen. The literature on gliosarcomas arising in brain tumors other than high-grade gliomas is reviewed.

Cell Transformation, Neoplastic↗

Multiple branchial cleft-like cysts in Hashimoto's thyroiditis.

We report two cases of multiple intrathyroidal cysts in women with Hashimoto's thyroiditis. The cysts were lined by squamous and focally columnar epithelium, and they were surrounded by follicular lymphoid tissue and a fibrous capsule. They appeared similar to branchial cleft cysts of the lateral neck and were distinct from previously reported types of thyroid cysts. Although the histogenesis of these lesions is unclear, they are probably derived from developmental rests. A relationship between the cystic enlargement of these rests and the Hashimoto's disease seems likely.

Branchioma↗

Primary intracranial leiomyosarcoma. Case report.

A case of primary intracranial leiomyosarcoma is presented, with clinical, radiological, light microscopic, immunohistochemical, and ultrastructural data. The histogenesis is discussed and the literature on smooth-muscle tumors of the central nervous system is reviewed.

Aged↗

Retrovirus-mediated gene therapy of experimental brain neoplasms using the herpes simplex virus-thymidine kinase/ganciclovir paradigm.

Recent results in experimental brain tumors indicate that transfer of sensitizing genes to tumor cells in vivo with subsequent drug treatment can reduce tumor masses and prolong the survival of rodents. In the present study, the 9L rat gliosarcoma model was used to evaluate the therapeutic effectiveness of the herpes simplex virus-thymidine kinase (HSV-tk) gene, delivered by a retrovirus vector, against tumor cells in the rat brain after systemic application of the nucleoside analogue ganciclovir (GCV). The HSV-tk gene was inserted into a retroviral vector (pMFG), which was produced using the amphotropic packaging cell line CRIP-MFG-S-HSV-TK. Packaging cells were implanted into established 9L tumors in the brains of syngeneic rats to effect gene delivery to tumor cells, followed by intraperitoneal GCV injections. Treated animals survived significantly longer (more than twice as long) than did the control groups. Brains from GCV-treated and nontreated animals were examined immunohistochemically at different time intervals after grafting of CRIP-MFG-S-HSV-TK cells and GCV treatment. Tumors in GCV-treated animals were significantly smaller as compared with nontreated animals at all time points. Sections stained immunohistochemically for HSV-TK confirmed gene transfer to tumor cells, which could be distinguished from packaging cells by different morphology and immunohistochemical staining for the retroviral envelope protein gp70. Approximately 45% of the cells in tumors implanted with CRIP-MFG-S-HSV-TK cells, but not treated with GCV, showed immunocytochemical staining for HSV-TK, demonstrating a high-efficiency of retrovirus-mediated gene transfer. Tumors in rats treated with packaging cells and GCV showed only 9% HSV-TK-positive cells after treatment, indicating that most cells expressing the HSV-tk gene were killed. The success of this therapeutic modality in experimental animals depends in large parts on the high efficiency of gene delivery and on the immune response against tumor cells.

Animals↗