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Biomedical subjects

R A Danks

Publications and source records attributed to R A Danks.

8 recordsLinked to original sources
PubMed2000

Craniotomy under local anesthesia and monitored conscious sedation for the resection of tumors involving eloquent cortex.

OBJECTIVE: Resection or even biopsy of an intra-axial mass lesion in close relationship to eloquent cortex carries a major risk of neurological deficit. We have assessed the safety and effectiveness of craniotomy under local anesthesia and monitored conscious sedation for the resection of tumors involving eloquent cortex. METHODS: We have performed a retrospective review of a consecutive series of 157 adult patients who underwent craniotomy under local anesthesia by one surgeon (P.M.B.) at Brigham and Women's Hospital in Boston. All patients had tumors in close proximity to eloquent cortex, including speech, motor, primary sensory, or visual cortex. In most cases the lesion was considered inoperable by the referring surgeon. All resection was verified by post-operative imaging approximately one month after surgery and all cases were reviewed by an independent neurosurgeon (A.D.). RESULTS: In 122 cases, brain mapping was performed to identify eloquent cortex and in the remainder neurological monitoring was maintained during the procedure. Radiological gross total resection was achieved in 57% of patients and greater than 80% resection was achieved in 23%. Thus 4 out of 5 of patients had major resection despite the close relationship of tumor to eloquent cortex. In 13%, less than 80% of tumor was removed because of danger of neurological deficit. In 7% of patients, only a biopsy could be done because of infiltration into eloquent cortex that could only be assessed at surgery. In 76 patients with pre-operative neurological deficits, there was complete resolution of these deficits in 33%, improvement in 32%, no change in 28%, and long-term worsening in 8%. Among 81 patients with no pre-operative neurological deficit, 1 patient suffered a major permanent neurological deficit, and 2 developed minor deficits. There was a transient post-operative deficit in one-third of cases, but this had resolved at one month in all but three patients. Monitored conscious sedation was performed without anesthetic complications using midazolam, sufentanyl and fentanyl with or without propofol. Only one case needed to be converted to general anesthesia. Patient satisfaction with the procedure has been good. Operating time and hospital stay were lower than the mean for brain tumor craniotomy at this hospital. CONCLUSIONS: Tumor surgery with conscious sedation is a safe technique that allows maximal resection of lesions in close anatomical relationship to eloquent cortex, with a low risk of new neurological deficit. Only 7% of intrinsic cortical tumors were ineligible for partial or complete resection with this technique.

Adolescent↗
PubMed2000

Growth and migration markers of rat C6 glioma cells identified by serial analysis of gene expression.

Tumors derived from rat C6 cell implants into rat brain exhibit similar morphological characteristics and degree of vascularization to human glioblastomas. To establish a molecular basis for C6 gliosarcoma malignancy, we have constructed a molecular profile of the most abundantly expressed genes, using serial analysis of gene expression (SAGE). Sequence tags (1168) representing 738 individual transcripts were collected and tag-to-gene mapping was carried out using the UniGene data set for rat. Differentially expressed C6 transcripts were identified by comparison of tags collected for C6 cells with a similar number (1002) of tags from a rat primary astrocyte library. Genes found to be expressed at increased levels in C6 cells are associated with cell surface interactions, migration, or metastasis formation and proliferation. These include the receptor for hyaluronan-mediated motility (RHAMM), S-100 related protein 42A, galectin I, preproenkephalin, osteopontin, autocrine motility factor, alpha-tubulin, ad1 antigen, and cofilin. In addition, a tag with no database match probably representing a previously uncharacterized transcript was differentially expressed in C6 cells. Transcripts showing reduced expression in C6 cells relative to astrocytes included the extracellular matrix glycoprotein osteonectin/SPARC (secreted protein, acidic, rich in cysteine), actin-binding proteins thymosins beta-4 and beta-10, the cysteine protease inhibitor cystatin C, the actin-gelling protein SM22/transgelin, and ferritin-H. SAGE results were confirmed by Northern blot for all transcripts tested, reaffirming the value of the SAGE technique for expression profiling in cancer biology.

Animals↗
PubMed1998

Patient tolerance of craniotomy performed with the patient under local anesthesia and monitored conscious sedation.

OBJECTIVE: Craniotomy and brain mapping performed with the patient under local anesthesia and monitored sedation is an important technique to allow optimal resection of brain tumors or other lesions in close apposition to eloquent cortex. The subjective experience of patients undergoing this procedure has not been addressed in the literature. METHODS: This study formally, intensively, and prospectively assessed the subjective experience of 21 consecutive patients undergoing this procedure. Assessment involved structured interviews at 2 to 3 days postoperatively by a member of the surgical team and at 1 month postoperatively by a psychiatrist, supplemented by pre- and postoperative assessments of the patients' moods using the brief Profile of Mood States questionnaire. RESULTS: At the 1-month interview, all patients were entirely comfortable with the experience and there were no indications of adverse psychological sequelae of the event. In the early postoperative interview, approximately one-half of the patients reported that the experience was entirely satisfactory, without any intraoperative discomfort or pain. One-third of the patients recalled minor difficulties at some stage of the experience, and one-fifth recalled moderate difficulties. An operating room score was devised to quantify the data. Minor technical changes are suggested to improve the patients' subjective experience. CONCLUSIONS: This series confirmed that this technique is a very useful and safe technique for resection of lesions involving eloquent cortex that might otherwise be considered inoperable. This procedure involves a level of stress that remains within the tolerance level of the average adult.

Adult↗
PubMed1995

Transformation of astrocytes in transgenic mice expressing SV40 T antigen under the transcriptional control of the glial fibrillary acidic protein promoter.

There are many animal models of glioma, but few that represent the biology of low-grade tumors and allow the study of the genetic mechanisms of glial oncogenesis. We report the in vivo transformation of astrocytic cells in transgenic mice by the SV40 T antigen under the control of the 5'-flanking sequence of the murine glial fibrillary acidic protein (GFAP) gene. High levels of T antigen expression were detectable in a tissue distribution that mirrored the normal expression of GFAP. This was associated with a consistent phenotype in the founder mice. Diffuse proliferation occurred in cells of the periventricular subependymal zone with diffuse invasion into the brain parenchyma, leading to death by 19-30 days postnatally. Transformed cells exhibited secondary structuring, a typical histopathological feature of human astrocytomas. Early passage cultures of these cells expressed GFAP in vitro and were transformed on the basis of tumor formation after transplantation into nude mice. These results demonstrate the susceptibility of periventricular astrocytic cells in the immature brain to malignant transformation. Furthermore, this study demonstrates the potential of the transgenic approach for the in vivo determination of genetic events involved in astrocyte transformation and for the development of novel models of astrocytoma.

Animals↗
PubMed1995

Aberrant p53 expression does not correlate with the prognosis in anaplastic astrocytoma.

Mutations of the p53 tumor-suppressor gene, as determined by the immunohistochemistry of archival formalin-fixed specimens, have been correlated with the prognosis for patients with many different types of malignancy. Similar correlations have been shown in series including patients with all grades of astrocytoma. We hypothesized that this might be a clinically useful prognostic indicator for patients with a defined grade of astrocytoma, anaplastic astrocytoma. This series comprised 54 consecutive patients with biopsy-proven anaplastic astrocytoma treated at one institution. When the CM-1 antiserum was used for testing, 33 (61%) of the 54 biopsies exhibited positive nuclear staining for p53, indicating an abnormal accumulation of the protein. This staining was graded according to the number of positive cells per high-power field. Positive immunohistochemical staining for p53 in the tumor cell nuclei did not correlate with the patient's outcome. Significant correlates of improved patient survival were the presentation with epilepsy in the absence of a neurological deficit (P = 0.005) and the surgeon's performance of a macroscopically complete surgical resection of the tumor (P = 0.01).

Adult↗
PubMed1993

Experience with nimodipine in aneurysmal subarachnoid haemorrhage.

OBJECTIVES: To assess the efficacy of nimodipine in preventing delayed ischaemic deficit in aneurysmal subarachnoid haemorrhage. DESIGN: A continuous prospective audit of all patients with aneurysmal subarachnoid haemorrhage admitted to the joint neurosurgery units of Prince Henry's and Alfred hospitals, Melbourne. Patients were divided into two groups--135 in the pre-nimodipine group during 1986 to 1989, and 73 in the nimodipine group during 1989 and 1990. MAIN OUTCOME MEASURES: Outcome was measured according to the Glasgow outcome scale and the incidence of delayed ischaemic deficit was recorded. RESULTS: A substantial reduction in the overall incidence of poor outcome was observed, from 37% of patients in the non-nimodipine group, to 20% in the nimodipine group (P = 0.022). Delayed ischaemic deficit occurred in 41% and 21% (P = 0.005), and poor outcome due to delayed ischaemic deficit occurred in 18% and 8% (P = 0.09) respectively. CONCLUSIONS: In our experience, nimodipine appears to have substantially reduced the incidence of delayed ischaemic deficits in patients with aneurysmal subarachnoid haemorrhage, with a resultant improvement in overall patient outcome.

Brain Ischemia↗
PubMed1988

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS): adolescent onset with severe cerebral edema.

A 19-year-old woman with long-standing sensorineural deafness, bilateral cataracts and mild clumsiness, presented with acute focal edema in the left temperoparieto-occipital area which required surgical decompression as a life-saving measure. Investigation revealed a persistent lactic acidemia and evidence of many ragged red fibres in a skeletal muscle biopsy specimen, suggesting a diagnosis of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome. The patient developed two further stroke-like episodes over a short period. One sibling died at the age of 14 years with a progressive neurological illness characterised by seizures, bilateral optic atrophy, ataxia, myoclonus and progressive dementia. The diagnosis of MELAS syndrome should be considered in young people presenting with stroke-like episodes that fail to conform to a given vascular territory, particularly if they have long-standing minor neurological abnormalities or a family history of obscure early onset neurological disease. The different clinical pictures in the two affected siblings in this family suggest that MELAS syndrome is part of a spectrum of inherited mitochondrial cytopathies rather than a discrete disease entity.

Acidosis, Lactic↗