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Biomedical subjects

W S Poon

Publications and source records attributed to W S Poon.

At least 91 records · Page 5Linked to original sources

Transcranial Doppler ultrasonography (TCD) in ventilated head injured patients: correlation with stable xenon-enhanced CT.

Disturbance of cerebral vasomotor regulation has been shown to be associated with the severity of traumatic brain injury (TBI). The transient hyperaemic response (THR) test is a test of the pressure autoregulatory response in terms of cerebral blood flow velocity after a brief carotid artery compression. Correlating with the test of cerebral vascular reactivity (CVR) to carbon dioxide by means of passive hyperventilation suggested that the THR test is a simple clinical test for the assessment of cerebral haemodynamic status in head-injured patients.

Adolescent↗

The impact of acute hyponatraemia on severe traumatic brain injury in rats.

The effect of experimental acute hyponatraemia on severe traumatic brain injury (TBI) was studied in a modified impact-acceleration model. The cortical contusional volume was quantified by image analysis on serial sections, injured axons were visualized and quantified by beta-Amyloid Precursor Protein (beta-APP) immunohistochemical staining. Regional brain water content was estimated by the wet-dry weight method. The experiment was conducted in Group I (injury only) and Group II (injury followed by acute hyponatraemia). Comparison between the two groups showed that acute hyponatraemia significantly increased contusional volume (3.24 +/- 0.70 mm3 vs. 1.80 +/- 0.65 mm3, P = 0.009) and the number of injured axons (128.7 +/- 44.3 vs. 41.7 +/- 50.1, P = 0.04) in the right thalamus & basal ganglia region. Water content of the brain stem region was also significantly increased by acute hyponatraemia (73.71 +/- 0.14% vs. 72.28 +/- 0.93%, P = 0.004). These results suggest that acute hyponatraemia potentiates secondary brain damage in severe TBI by augmentation of both focal contusion and diffuse axonal injury. The injured brain stem region is more susceptible to edema formation induced by experimental acute hyponatraemia.

Amyloid beta-Protein Precursor↗

Telomere length and telomerase catalytic subunit expression in non-astrocytic gliomas.

Telomerase activation has been implicated as a major factor in the development of cancer. In our previous study we reported on the telomerase activity of a variety of gliomas. To further investigate the role of telomere and telomerase regulation in the pathogenesis of non-astrocytic gliomas, we examined the telomere length and the mRNA expression of telomerase reverse transcriptase gene (hTERT) and telomerase-associated protein (hTEP) in a series of 27 oligodendroglial and 18 ependymal tumors in this study. No statistical difference was found between the mean telomere length in telomerase-positive and telomerase-negative tumors (11.5 kb vs 13.1 kb; p = 0.424), although a slightly shorter length was observed in telomerase-positive oligodendroglial tumors. mRNA expression of hTERT was highly correlated with the telomerase activity status. hTERT was expressed in 8/8 (100%) and 2/2 (100%) telomerase-positive oligodendroglial and ependymal tumors, respectively, whereas 3/6 (50%) telomerase-negative oligodendroglial tumors and no telomerase-negative ependymal tumors showed expression. In contrast, hTEP1 mRNA was widely expressed in both telomerase-positive and telomerase-negative oligodendroglial and ependymal tumors. Our data support the notion that hTERT plays a critical role in determining the enzymatic activity of human telomerase. It has recently been proposed that both p16(INK4)/Rb pathway inactivation and telomerase activity were required for immortalization of epithelial cells. Although lack of p(16INK4a) expression was detected in a substantial proportion of tumors, no correlation between the p16(INK4a) or pRb protein expression and telomerase activity was observed in our series of non-astrocytic tumors.

Adolescent↗

Central neurocytomas are genetically distinct from oligodendrogliomas and neuroblastomas.

AIMS: Central neurocytoma is a rare central nervous system tumour typically found in the lateral ventricles and at the septum pellucidum. Histologically, it resembles oligodendrogliomas and yet ultrastructurally, it shows neuronal differentiation. Its molecular oncogenesis is not known. The aim of this study was to examine whether major genetic events found in oligodendrogliomas and neuronal tumours, namely allelic deletions of chromosomes 1p and 19q and N-myc amplification, can be found in central neurocytomas. As there was one report describing gain of chromosome 7 in central neurocytomas, we also examined epidermal growth factor receptor (EGFR) amplification, as the EGFR gene is located at chromosome 7p. METHODS AND RESULTS: Nine central neurocytomas and matched blood samples were examined for loss of heterozygosity (LOH) of 1p and 19q13.2-13.4 with 23 finely mapped microsatellite markers. N-myc amplification was studied by fluorescence in-situ hybridization using paraffin-embedded sections. EGFR amplification was tested for by differential PCR. Six of nine (67%) tumours showed LOH at one or more loci at 1p and 5/9 (56%) of cases showed LOH at 19q. However, common regions of deletion cannot be identified. The majority of informative markers are retained at 1p (84%) and 19q (86%). Only one tumour showed amplification of N-myc and none of the cases showed amplification of EGFR. CONCLUSION: Central neurocytomas are genetically distinct from oligodendrogliomas, and chromosomes 1p and 19q probably do not play an important role in their pathogenesis. N-myc and EGFR amplification are rare.

Adolescent↗

Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas.

AIMS: While it is well known that pilocytic astrocytomas are clinically distinct from diffuse astrocytomas, few comprehensive studies have focused on their genetic differences. The aim of this study was to examine pilocytic astrocytomas for genetic alterations that are commonly seen in diffuse astrocytomas. METHODS AND RESULTS: By using molecular genetic and immunohistochemical techniques, we evaluated p16, p53, CDK4 and PTEN genes in 29 pilocytic astrocytomas. Mutation screening of p53 and PTEN was performed by single strand conformation polymorphism analysis followed by direct sequencing. Loss of heterozygosity (LOH) of p53, p16 and 10q23-25 loci was performed with microsatellite markers and genomic microsatellite instability (MSI) was also screened. Protein expression of p16, p53, CDK4 and PTEN was examined by immunohistochemistry. Five tumours were found to have single genetic alterations, which included a p53 mutation, a PTEN mutation, MSI at a single microsatellite marker of the p16 locus, and one single LOH at each p16 and 10q23 loci. Protein expressions of p16, CDK4 and PTEN were detected in 73%, 61% and 38% of tumours, respectively. Significantly and in sharp contrast to diffuse astrocytomas, no pilocytic astrocytoma in our series stained for p53 protein. CONCLUSION: Pilocytic astrocytomas have neither MSI phenotype nor recurrent alterations of the p53 and p116 genes. However, altered expression of PTEN may be important in the genesis of pilocytic astrocytomas. We conclude that pilocytic astrocytomas are genetically distinct from diffuse astrocytomas. Lack of p53 mutation/immunostaining may serve as a diagnostic adjunct for differentiating pilocytic astrocytomas from diffuse astrocytomas in small neurosurgical biopsies.

Adolescent↗

Metastatic solitary fibrous tumor of the meninges. Case report.

Solitary fibrous tumor (SFT) is a unique tumor composed of interstitial dendritic cells that was first described in the thorax and subsequently reported in diverse organs. Extrathoracic SFTs are predominantly benign but rare malignant cases have been documented. In the nervous system, SFT has been described as a meningeal lesion although all 14 previously reported cases were benign. The authors report the first case of a meningeal SFT occurring in a 55-year-old woman. The tumor first presented as a meningeal lesion that after three recurrences over a 10-year period metastasized to the soft tissues and lungs. The potentially malignant nature of cranial SFTs, especially those with atypical histological features and high mitotic counts, should be recognized.

Female↗

Genetic alterations in pediatric high-grade astrocytomas.

High-grade astrocytomas are tumors that are uncommon in children. Relatively few studies have been performed on their molecular properties and so it is not certain whether they follow different genetic pathways from those described in adult diffuse astrocytomas. In this study, we evaluated 24 pediatric high-grade astrocytomas (11 anaplastic astrocytomas and 13 glioblastomas) all of which were sporadic and primary. We studied mutations of p53, phosphatase and tensin homolog (PTEN), loss of heterozygosity (LOH) of chromosomes 17p13, 9p21 and 10q23-25, amplification of epidermal growth factor receptor (EGFR), and overexpression of EGFR and p53 protein. In addition, we searched for microsatellite instability (MSI) by using MSI sensitive and specific microsatellite markers. p53 mutations were found in 38% (9/24) of the high-grade astrocytomas and all brain stem tumors except 2 (71%, 5/7) had p53 mutations. PTEN mutations were found in 8% (2/24) of high-grade astrocytomas. However, no EGFR amplification was found in any of them. LOH was found at 17p13.1 in 50% (3/6 informative tumors), 9p21 in 83% (5/6 informative tumors), and 10q23-25 in 78% (7/9 informative tumors). Four tumors showed MSI, and 2 of them that showed widespread MSI were regarded as tumors with replication error (RER+) phenotype. All 4 tumors with MSI showed concurrent LOH of 9p21 and 10q23-25. Combining gene alterations, LOH, MSI, and gene mutations, inactivation of both alleles of PTEN and p53 was found in 57% (4/7 informative tumors) and 50% (3/6 informative tumors) of the cases respectively. We conclude that development of pediatric high-grade astrocytomas may follow pathways different from the primary or secondary paradigm of adult glioblastomas. In a subset of these tumors, genomic instability was also implicated.

Adolescent↗

Far lateral approach with intraoperative ultrasound Doppler identification of the vertebral artery.

A 69-year-old woman presented with right hemiparesis and magnetic resonance imaging revealed a meningioma at the ventral aspect of the foramen magnum. We used a retromastoid curvilinear incision down the lateral aspect of the neck to expose the semispinalis and other muscles. Guided by ultrasound to avoid damage to the vertebral artery beneath the semispinalis, we incised the semispinalis muscle in a U-shape that hinged at the retromastoid curvilinear incision with its one limb along the border of the foramen magnum and the other limb along the posterior arch of the atlas. The other muscles were divided in line with the curvilinear incision and retracted posteriorly with the bulk of semispinalis to expose the bones, not disturbing the U-shaped piece of semispinalis that covered the vertebral artery. Similarly guided by ultrasound, we performed far lateral suboccipital craniectomy and laminectomy, exposed the dura above and below the dural entry of the vertebral artery, opened the dura cephalad and caudal to the dural entry of the vertebral artery, and excised the tumor. This method provided adequate exposure to the lateral aspect of the cranio-vertebral junction and minimized the risks of dissecting the whole extradural segment of vertebral artery. It requires more cases to determine whether the results of this patient can be generalized.

Aged↗

Diffuse leptomeningeal gliomatosis with oligodendroglioma.

Leptomeningeal gliomatosis is a primary glioma residing mainly in the leptomeninges. We describe a rare case of diffuse leptomeningeal glioma, occurring in a six year old girl, in which the morphological features of the cellular infiltrates were those of an oligodendroglioma. To our knowledge, this is the fifth case of diffuse oligodendrogliomatosis reported in the English language literature.

Biomarkers, Tumor↗

Propofol requirement is decreased in patients with large supratentorial brain tumor.

BACKGROUND: The anesthetic requirement is decreased in animals with head injury, but there are no data regarding the effect of intracranial tumor on the potency for intravenous anesthetics. The authors compared the quantal dose-response curves for propofol in patients having large (> or = 30 mm, mass effect) brain tumor with those having smaller (< 30 mm) lesions and with control patients undergoing noncranial surgery. METHODS: Sixty patients in each group were randomly assigned to receive one of the six doses of propofol (0.5, 0.7, 1.0, 1.3, 1.8, or 2.5 mg/kg) over 10 s. Two minutes after drug administration, patients were asked to open their eyes as a test for response to verbal command. Patients who failed to respond were given a 10-s, 50-Hz, 80-mA transcutaneous tetanic electrical current to the ulnar nerve as a test for response to painful stimulus. Purposeful movement indicated positive response. Log dose-response curves for loss of response to verbal command and tetanic stimulus were calculated after logit transformation. RESULTS: The median effective doses (ED50s; 95% confidence interval) for suppressing response to verbal command and tetanic stimulus were 0.75 (0.65-0.86) mg/kg and 1.28 (1.11-1.49) mg/kg, respectively, in patients with large brain tumor. These values were significantly less than the corresponding ED50s in patients with small tumor, 1.01 (0.88-1.15) mg/kg and 1.76 (1.51-2.07) mg/kg, or healthy control subjects, 0.98 (0.86-1.12) mg/kg and 1.89 (1.62-2.23) mg/kg. CONCLUSIONS: The doses of propofol required to suppress response to verbal command and tetanic stimulus were 23% less and 32% less in patients with large brain tumor compared with control subjects. Small tumor did not affect potency of propofol.

Adolescent↗

Cerebellar astrocytoma associated with von Hippel-Lindau disease: case report with molecular findings.

We describe the rare occurrence of a cerebellar astrocytoma developing in a patient with the von Hippel-Lindau disease. This tumour possessed well-differentiated fibrillated astrocytes and moderate vascular proliferation. Tumour cells were uniformly GFAP positive and negative for lipids. This tumour showed an A to C mutation at nucleotide 675 at the splicing donor site of exon 2 of the VHL gene and a concurrent loss of heterozygosity of the 3p25 locus, a site of allelic deletions reported in some astrocytomas. Allelic loci at 17q11, a site of common loss in pilocytic astrocytoma, however, were retained in this tumour. This case illustrates that astrocytomas are rarely found in the von Hippel-Lindau disease and they may contain genetic changes common to both haemangioblastomas and some astrocytomas.

Adult↗

CSF antibiotic prophylaxis for neurosurgical patients with ventriculostomy: a randomised study.

The value of prophylactic antibiotics for patients with ventricular catheter for monitoring and CSF drainage is uncertain. 228 patients were randomised to receive perioperative antibiotics only (Unasyn, Group I) or prolonged antibiotics for the presence of the ventricular catheter (Unasyn and Aztreonam, Group II). The incidence of intracranial and extracranial infection was documented prospectively. Group II patients had a significantly reduced incidence of CSF infection [3/115 (3%) vs 12/113 (11%), p = 0.01] and extracranial infections [23/115 (20%) vs 48/113 (42%), p = 0.002]. CSF pathogens in Group II patients were MRSA and Candida, whereas in Group I, Staphylococci, E coli and Klebsiella. Although prolonged antibiotic prophylaxis significantly reduced the incidence of serious CSF infection as well as extracranial infections, this policy did select resistant or opportunistic pathogens such as Candida and MRSA.

Adolescent↗

Telomerase expression in gliomas including the nonastrocytic tumors.

Telomerase is a ribonucleoprotein that consists of a RNA component for synthesizing telomeric DNA repeats onto chromosome ends, so that telomere length can be maintained; telomerase activation in general signifies immortalization of cells. Because the telomerase activity of only a few cases of nonastrocytic gliomas and low-grade astrocytic gliomas have been examined before, telomerase activity from a broad spectrum of astrocytic and nonastrocytic gliomas were examined in this study. A total of 119 brain tumor samples, including 16 pilocytic astrocytomas, one dysembryoplastic neuroepithelial tumor (DNT), two pleomorphic xanthoastrocytomas (PXA), 15 ependymomas, 21 oligodendrogliomas, 13 grade II astrocytomas, 13 anaplastic astrocytomas, and 38 glioblastoma multiforme tumors (GBM), were studied, using a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol assay. All pilocytic astrocytomas, DNT, PXA, and myxopapillary ependymomas were telomerase negative. Three of 13 (15.4%) classical ependymomas, 2 of 14 (14.3%) grade II oligodendrogliomas, and three of seven (42.9%) anaplastic oligodendrogliomas had detectable telomerase activity. The frequency of telomerase expression in ependymomas and oligodendrogliomas was lower than those observed in astrocytic tumors: fibrillary astrocytoma, 23.1%; anaplastic astrocytoma, 23.1%; and GBM, 26.3%. The mean age of telomerase-positive GBM patients (61.7 years) was significantly higher than that of telomerase-negative GBM patients (47.8 years, P=.002). These results suggest that telomerase activation may occur early in glial tumorigenesis, and astrocytomas may have mechanisms of immortalization other than telomerase activation.

Adolescent↗

Analysis of cell cycle regulators: p16INK4A, pRb, and CDK4 in low- and high-grade meningiomas.

Abnormalities in the p16INK4A, CDK4, and Rb genes, which regulate transition through G1 phase of the cell cycle, have been implicated in the progression of diverse types of cancer. To evaluate the involvement of p16INK4A, CDK4, and Rb in the tumorigenesis of meningiomas, the status of these genes or gene products were examined. The genetic alteration of the p16INK4A gene was examined by homozygous deletions and by mutation analysis. The methylation status of the p16INK4A was determined by Southern blotting. Neither homozygous deletions nor point mutations of the p16INK4A gene were observed in any of the 23 meningiomas. Partial rather than complete methylation of the p16INK4A gene at SacII or SmaI sites was shown in five (23.8%) meningiomas. The methylation status of the p16INK4A gene was not consistently associated with the expression of p16INK4A in meningiomas. These results suggest that the true relationship between methylation and expression of p16INK4A may be obscured in a complex manner by various mechanisms that regulate p16INK4A expression. Aberrant expressions of pRb and CDK4 were not observed in any of the meningiomas we examined, indicating that abnormalities of the pRb and CDK4 appear to be rare in meningiomas.

Adolescent↗

Recombinant tissue plasminogen activator for the treatment of spontaneous adult intraventricular hemorrhage.

BACKGROUND: Intraventricular hemorrhage (IVH) has a poor prognosis with mortality rates of between 80 and 100% when all four ventricles are involved. Fibrinolytic therapy has been reported to improve overall outcome. METHODS: Patients with severe primary IVH were treated by direct intraventricular injection of recombinant tissue plasminogen activator (rt-PA) into the lateral ventricles, followed by cerebrospinal fluid (CSF) drainage if the intracranial pressure rose above 20 mm Hg. RESULTS: Over a 15-month period from 1995 through 1996, 10 patients were treated, (4 male and 6 female, mean age 35 years; range, 21-55 years). The mean Glasgow Coma Scale score on admission was 6 (range, 4-8) and the mean Graeb score for severity of IVH on the first CT scan was 10 (range, 8-12). Angiography was negative in five cases but identified arteriovenous malformations in three, a post-traumatic pseudoaneurysm in one, and Moya-moya disease in one. The mean total dose requirement of rt-PA was 8.25 mg (range, 6-12 mg) with a significant reduction in the mean Graeb score after 7 days to 3.9 (range, 2-7, p<0.0001). Outcome at 3 months was death in one case (mortality 10%), severe disability in two (20%), moderate disability in three (30%), and good result in four (40%). Four patients (40%) required subsequent CSF shunting. No complications of rehemorrhage, infection, or catheter obstruction were encountered. CONCLUSION: Intraventricular fibrinolysis with rt-PA seems to be safe and effective for the treatment of severe IVH.

Adult↗

A comparison of the Hamamatsu NIRO 500 and the INVOS 3100 near-infrared spectrophotometers.

Near-infrared spectroscopy is a technique used for non-invasive measurement of cerebral oxygenation and a number of commercial devices are currently available for use. We compared measurements of cerebral oxygenation made with two near-infrared spectrophotometers--the Somanetics Invos 3100 cerebral oximeter and the Hamamatsu NIRO-500 near-infrared spectrophotometer. Hypoxia was induced in six healthy male volunteers with and without occlusion of scalp blood flow. Oxygen saturation, end-tidal carbon dioxide tension, regional cerebral oxygen saturation, change in regional cerebral oxyhaemoglobin concentration and change in regional cerebral total haemoglobin concentration were measured. The INVOS 3100 displays cerebral oxygen saturation directly. The NIRO-500 displays change in total haemoglobin concentration and oxyhaemoglobin concentration, and the cerebral oxygen saturation was calculated offline. Statistical analysis disproved the assumption that the INVOS 3100 and the NIRO-500 were measuring the same changes in cerebral oxygenation. Neither machine can be confirmed for reliability against a gold standard and operational difficulties mean that neither can be recommended for routine clinical use.

Brain↗

Primary leptomeningeal astrocytoma. Case report.

Gliomas very rarely arise from the leptomeninges. They can be both solitary and diffuse, and histological examination reveals mostly astrocytic tumors. The authors report a case (the 12th reported in the literature) of a solitary primary glioma of the leptomeninges in a 79-year-old man who presented with repeated seizures. A magnetic resonance image revealed an ill-defined enhancing lesion in the cerebral meninges. Autopsy examination showed a poorly demarcated astrocytoma in the sylvian fissure infiltrating the adjacent subarachnoid space. The literature concerning primary leptomeningeal glioma is reviewed.

Aged↗