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Biomedical subjects

R R Hammond

Publications and source records attributed to R R Hammond.

At least 19 recordsLinked to original sources
PubMed2005

Spontaneous remyelination following prolonged inhibition of alpha4 integrin in chronic EAE.

Inhibition of alpha(4)beta(1) integrin blocks immune cell influx into the CNS providing benefit to patients with multiple sclerosis and in animal model systems. We have used this mechanism to examine whether the presence of inflammatory cells suppresses spontaneous myelin repair in experimental autoimmune encephalomyelitis. We observed (1) 87% of plaques showed remyelination after 40 days of treatment; (2) myelin repair occurred in half of the total lesion area; (3) half of the animals regained motor function. There was no significant repair or gain of motor function in vehicle-treated animals. Therefore, prolonged inhibition of CNS inflammation, in the absence of targeted myelin repair, facilitates mechanisms of spontaneous remyelination.

Animals↗
PubMed2004

Myoclonic status epilepticus following repeated oral ingestion of colloidal silver.

The authors report a case of a 71-year-old man who developed myoclonic status epilepticus and coma after daily ingestion of colloidal silver for 4 months resulting in high levels of silver in plasma, erythrocytes, and CSF. Despite plasmapheresis, he remained in a persistent vegetative state until his death 5.5 months later. Silver products can cause irreversible neurologic toxicity associated with poor outcome.

Adenocarcinoma↗
PubMed2001

Wartenberg's migrant sensory neuritis.

We describe a patient with the sudden onset of a painful, purely sensory, mononeuritis multiplex. Investigations showed no evidence for any underlying systemic condition. A nerve biopsy showed fascicular wallerian degeneration with perineurial thickening, inflammatory cells, and immunoglobulin G (IgG) deposition. His painful sensory deficits persisted, with no improvement after treatment with prednisone. The clinical characteristics in this case were very similar to those originally described by Wartenberg, and subsequently by other investigators. The investigations in our case strongly suggest that there may be an underlying immune pathogenesis for cases of Wartenberg's migrant sensory neuritis.

Adult↗
PubMed2001

June 2001: 61 year old woman with confusion and obtundation.

The June COM. A 61 year old female presents with a three week history of increasing confusion, lethargy and headache. A neurological exam revealed disorientation, mild expressive aphasia, bilateral papilledema, and a right pronator drift. She had a craniotomy and resection of tumor. The tumor histologically was consistent with a solitary fibrous tumor displaying malignant features of hypercellularity, marked nuclear atypia, high mitotic activity, and a high proliferation index. This case is unique as the first malignant variant of solitary fibrous tumor to be reported intracranially.

Antigens, CD34↗
PubMed2001

Nestin expression in cortical dysplasia.

OBJECT: It is recognized that cortical dysplasia (CD) is associated with an increased incidence of glioneuronal neoplasms. Among hypothetical considerations, there is the possibility that CD and other neuronal migration abnormalities harbor dysmature cells with the potential to give rise to glioneuronal neoplasms. Such cells, if present, would be reasonably expected to display immature features. The goal of the present study was to characterize the expression of nestin, a neuroepithelial precursor/stem cell antigen, in CD, along with other pathological and clinical features of this entity. METHODS: Clinical and surgical features of 10 recent cases meeting the histological criteria for CD were reviewed. Expressions of nestin, MAP2, neurofilament, and glial fibrillary acidic protein (GFAP) were assessed using immunohistochemical analysis and confocal scanning laser microscopy. Immunoreactivity for both glial and neuronal antigens as well as nestin was found in a select group of cells within regions of CD. Immunohistochemical and confocal microscopic findings demonstrated that these cells with neuronal or ambiguous features are a mixed population, some of which are dysmature neurons (positive for nestin and MAP2), whereas others are astrocytic (positive for nestin and GFAP). CONCLUSIONS: Further insight into the nature of nestin-positive neurons may shed light on the cause and pathogenesis of the associated glioneuronal tumors and the accompanying chronic seizures.

Adolescent↗
PubMed2000

Metallothionein induction in human CNS in vitro: neuroprotection from ionizing radiation.

PURPOSE: There have been extensive studies on the regulation of metallothionein (MT) synthesis, and its biological role in liver and kidney. Although there are few reports on brain MT, there is a growing interest in the role of MT in brain. There have been no publications to date on MT synthesis in the human central nervous system (CNS) following exposure to ionizing radiation. In the present study, primary human CNS cultures were used to examine the effect of ionizing radiation on MT mRNA and protein synthesis. In the same cultures, the neuroprotective effects of zinc (Zn) and cadmium (Cd)-induced MT synthesis from high-dose radiation were also examined. MATERIALS AND METHODS: Primary, serum-free, human CNS cultures were exposed to 30 or 60 Gy gamma-rays. The total MT protein was then measured by a Cd-heme assay, and mRNA for MT-II and MT-III was detected by reverse transcription polymerase chain reaction (RT-PCR). Cytotoxicity was measured by LDH release and apoptotic cell death by DNA fragmentation analysis. Sublethal neuroglial injury was assessed morphologically using specific astrocytic (glial fibrillary acidic protein--GFAP) and neuronal (microtubule-associated protein 2--MAP2) immunohistochemical markers. RESULTS: The total MT protein content was increased 12h after exposure to 30Gy. The increase in MT content in response to 60Gy was not statistically significant. MT-II mRNA levels increased at 3 and 6h after exposure to 30Gy gamma-rays, with a maximum expression at 12-24 h. MT-III mRNA was not significantly affected. Exposure to 60 Gy, but not 30 Gy, caused a marked increase in LDH release. Cells exposed to 30 Gy or less showed some apoptotic cell death by DNA fragmentation analysis, while exposure to 60 Gy resulted in a DNA smear confirmed by LDH assays. Preinduction of MT by 5 microM Cd or 100 microM Zn resulted in a significant reduction in radiation-induced LDH release. Morphological evaluations revealed that Cd or Zn preincubation led to relative preservation of MAP2 staining and GFAP. CONCLUSION: Both MT protein and MT-II mRNA can be induced in human CNS cells by ionizing radiation. Furthermore, induction of MT synthesis with Zn and Cd can protect human CNS cells from radiation-induced cytocidal and sublethal injuries. Both findings have implications in the development of strategies to protect human CNS tissue from damage during radiotherapy.

Brain↗
PubMed2000

Malignant transformation of a dysembryoplastic neuroepithelial tumor. Case report.

A 29-year-old man presented in 1984 with a recent onset of partial seizures marked by speech arrest. Electroencephalography identified a left frontotemporal dysrhythmia. Computerized tomography (CT) scanning revealed a superficial hypodense nonenhancing lesion in the midleft frontal convexity, with some remodeling of the overlying skull. The patient was transferred to the London Health Sciences Centre for subtotal resection of what was diagnosed as a "fibrillary astrocytoma (microcystic)." He received no chemotherapy or radiation therapy and remained well for 11 years. The patient presented again in late 1995 with progressive seizure activity. Both CT and magnetic resonance imaging demonstrated a recurrent enhancing partly cystic lesion. A Grade IV astrocytoma was resected, and within the malignant tumor was a superficial area reminiscent of a dysembryoplastic neuroepithelial tumor (DNT). Data on the lesion that had been resected in 1984 were reviewed, and in retrospect the lesion was identified as a DNT of the complex form. It was bordered by cortical dysplasia and contained glial nodules, in addition to the specific glioneuronal element. The glial nodules were significant for moderate pleomorphism and rare mitotic figures. The Ki67 labeling index averaged 0.3% in the glial nodules and up to 4% focally. Cells were rarely Ki67 positive within the glioneuronal component. This case is the first documented example of malignant transformation of a DNT. It serves as a warning of the potential for malignant transformation in this entity, which has been traditionally accepted as benign. This warning may be especially warranted when confronted with complex forms of DNT. The completeness of resection in the benign state is of paramount importance.

Adult↗
PubMed1999

Oligodendroglioma: an appraisal of recent data pertaining to diagnosis and treatment.

OBJECTIVE: This article reviews and summarizes recent data on the diagnosis, prognosis, and treatment of oligodendroglial tumors. METHODS: Histological criteria for optimized diagnosis and grading of oligodendroglial tumors are described and discussed. The therapeutic approaches are analyzed in light of the results of recent series. RESULTS: Oligodendroglial tumors may be more common than is generally thought. Perinuclear halo and "chicken-wire" pattern, although considered classic histological features of oligodendrogliomas, are unreliable as sole criteria for diagnosis. Nuclear regularity and roundness and an eccentric rim of eosinophilic cytoplasm lacking obvious cell processes are more constant features. Grading should be accomplished using a composite of radiological and histopathological relevant features. The allelic loss of chromosome arms 1p and 19q might be a marker for both chemosensitivity and longer survival after chemotherapy. Oligodendrogliomas are notably chemosensitive when compared with other gliomas. For aggressive lesions, chemotherapy should be used upfront, after surgery. CONCLUSION: Oligodendrogliomas are underdiagnosed. One unfortunate implication is that a large number of patients may be receiving suboptimal care. A simplification in grading of oligodendroglioma to two grades would reduce the confusion surrounding the classification and better define prognosis and response to treatment modalities. A better definition of the so-called mixed tumor should also allow a better classification of these lesions in an intermediate prognostic class between astrocytic and oligodendroglial lesions. Loss of 1p and 19q could be used as a cytogenetic marker in assisting grading. New concepts emerging in the recent literature should help optimize the diagnosis of these lesions and reduce interobserver variability.

Brain↗
PubMed1998

Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas.

BACKGROUND/METHODS: Gliomas are common malignant neoplasms of the central nervous system. Among the major subtypes of gliomas, oligodendrogliomas are distinguished by their remarkable sensitivity to chemotherapy, with approximately two thirds of anaplastic (malignant) oligodendrogliomas responding dramatically to combination treatment with procarbazine, lomustine, and vincristine (termed PCV). Unfortunately, no clinical or pathologic feature of these tumors allows accurate prediction of their response to chemotherapy. Anaplastic oligodendrogliomas also are distinguished by a unique constellation of molecular genetic alterations, including coincident loss of chromosomal arms 1p and 19q in 50%-70% of tumors. We have hypothesized that these or other specific genetic changes might predict the response to chemotherapy and prognosis in patients with anaplastic oligodendrogliomas. Therefore, we have analyzed molecular genetic alterations involving chromosomes 1p, 10q, and 19q and the TP53 (on chromosome 17p) and CDKN2A (on chromosome 9p) genes, in addition to clinicopathologic features in 39 patients with anaplastic oligodendrogliomas for whom chemotherapeutic response and survival could be assessed. RESULTS/CONCLUSIONS: Allelic loss (or loss of heterozygosity) of chromosome 1p is a statistically significant predictor of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitivity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both chromosomes 1p and 19q were strongly associated with longer overall survival, whereas CDKN2A gene deletions and ring enhancement (i.e., contrast enhancement forming a rim around the tumor) on neuroimaging were associated with a significantly worse prognosis. The inverse relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma. These results suggest that molecular genetic analysis may aid therapeutic decisions and predict outcome in patients with anaplastic oligodendrogliomas.

Adult↗
PubMed1998

Case of the month: April 1998--30 year old male with perineal numbness.

A 30-year-old male presented with a 2 year progressive course of bowel and bladder dysfunction, mild leg weakness and sensory abnormalities in sacral dermatomes. MRI showed an intra-axial conus medullaris lesion which was excised and identified as a ganglioglioma. The case presents the typical clinical course and histopathology of this unusual lesion which carries a favorable prognosis after gross total removal. Preoperative neurological function in such patients is highly predictive of post-operative outcome.

Adult↗
PubMed1998

Fatal traumatic vertebral artery aneurysm rupture. Case report.

The authors present the case of a 34-year-old man struck over the left mastoid region by a hockey puck, who suffered a fatal rupture of a left vertebral artery berry aneurysm. He became apneic within seconds of the injury and had no brainstem reflex within minutes. The postmortem examination showed massive subarachnoid hemorrhage in the posterior fossa and the remnants of a berry aneurysm near the intradural origin of the left vertebral artery, 11 mm proximal to the posterior inferior cerebellar artery. Rupture of a saccular aneurysm as a result of head trauma is rare. This is the first reported case of a posterior circulation aneurysm rupture as a result of head trauma.

Adult↗
PubMed1998

Case of the month: June 1997--a 42 year old man with left facial weakness.

A 42 yr old male presented with left facial weakness. MRI showed lesions affecting the distal seventh nerve and third division of the trigeminal nerve. The seventh nerve was biopsied and showed a malignant epithelioid schwannoma. The patient underwent extensive resection followed by irradiation. This is one of very few examples of intracranial malignant peripheral nerve sheath tumors and the first reported example of an intracranial malignant epithelioid schwannoma. The literature is reviewed and completeness of resection appears to be the most pertinent prognostic factor.

Adult↗
PubMed1996

Cutaneous ganglioneuromas: a case report and review of the literature.

The occurrence of ganglioneuromas outside the sympathetic chains of the mediastinum and abdomen in the nonpediatric age group is rare. We report the case of a solitary cutaneous ganglioneuroma on the abdomen of a 52-year-old woman. The lesion, which had been present for 20 years, measured 1.2 cm in greatest dimension. Unmyelinated axons, Schwann cells, and scattered mature ganglion cells were identified by histochemistry, immunohistochemistry, and electron microscopy. Only three similar cases have been reported in the literature to date. Ganglioneuromas have also been reported as mature components of metastatic neuroblastomas and in association with plexiform neurofibromas, neither of which was present in this case. The pathogenesis of this lesion is unclear, however, aberrant migration of neural crest elements is the most likely explanation. The possible trophic role of sex steroids is also discussed. Although no follow-up series exist, local excision should he curative considering the small size and histologically benign appearance of the lesion.

Female↗
PubMed1995

Neuropathology of the retina in acquired immunodeficiency syndrome.

The pathogenesis of HIV-mediated neurodegeneration is unknown. Presently, work is focused on two main hypotheses: direct (caused by HIV or component proteins) versus indirect (monocyte-mediated) neurotoxicity. In HIV-induced retinal disease, the high incidence of opportunistic infections and the low HIV viral burden found in most clinical specimens present challenges in defining the roles played by potential factors. Future studies will see the resolution of these controversies by showing the mechanism of HIV-induced neuronal damage and its relationship to retinal disease.

Acquired Immunodeficiency Syndrome↗