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Biomedical subjects

T T Yeo

Publications and source records attributed to T T Yeo.

At least 19 recordsLinked to original sources
PubMed2001

The leukocyte common antigen-related protein tyrosine phosphatase receptor regulates regenerative neurite outgrowth in vivo.

Drosophila and leech models of nervous system development demonstrate that protein tyrosine phosphatase (PTP) receptors regulate developmental neurite outgrowth. Whether PTP receptors regulate neurite outgrowth in adult systems or in regenerative states remains unknown. The leukocyte common antigen-related (LAR) receptor is known to be present in rodent dorsal root ganglion (DRG) neurons; therefore, the well established model of postcrush sciatic nerve regeneration was used to test the hypothesis that LAR is required for neurite outgrowth in the adult mammalian nervous system. In uninjured sciatic nerves, no differences in nerve morphology and sensory function were detected between wild-type and LAR-deficient littermate transgenic mice. Sciatic nerve crush resulted in increased LAR protein expression in DRG neurons. In addition, nerve injury led to an increase in the proportion of LAR protein isoforms known to have increased binding affinity to neurite-promoting laminin-nidogen complexes. Two weeks after nerve crush, morphological analysis of distal nerve segments in LAR-deficient transgenic mice demonstrated significantly decreased densities of myelinated fibers, decreased axonal areas, and increased myelin/axon area ratios compared with littermate controls. Electron microscopy analysis revealed a significant twofold reduction in the density of regenerating unmyelinated fibers in LAR-/- nerves distal to the crush site. Sensory testing at the 2 week time point revealed a corresponding 3 mm lag in the proximal-to-distal progression of functioning sensory fibers along the distal nerve segment. These studies introduce PTP receptors as a major new gene family regulating regenerative neurite outgrowth in vivo in the adult mammalian system.

Animals↗
PubMed2001

Hypertensive basal ganglia hemorrhage: a prospective study comparing surgical and nonsurgical management.

BACKGROUND: The optimal treatment of hypertensive supratentorial intracerebral hemorrhage is still debated. Some studies have shown no improvement in survival or functional outcome after surgery when compared to conservative management while others have shown otherwise. METHODS: This study was a prospective trial, matching patients for hematoma volume and Glasgow Coma score on admission. RESULTS: There were a total of 34 patients. Seventeen were treated conservatively and 17 surgically. There was no significant difference between the two groups in terms of age, GCS, hematoma volume, or presence of intraventricular blood. At 3, 6, and 12-month follow-up, they were assessed using the Modified Barthel Index by a blinded observer. There was no difference between the two groups at 3, 6, or 12 months follow-up. The mortality rate was similar in the two groups. CONCLUSIONS: Based on this study and review of the literature, we cannot recommend routine evacuation of clots to treat these hemorrhages.

Adult↗
PubMed2001

Expression of the group I metabotropic glutamate receptor in the hippocampus of patients with mesial temporal lobe epilepsy.

Immunocytochemical studies at light and electron microscopic levels in hippocampi of patients with mesial temporal lobe epilepsy showed mGluR1 and mGluR5 immunoreactivity in the molecular layer of the dentate gyrus and CA1 area, especially at the border between stratum oriens and alveus. By electron microscopy, degenerating neuronal elements were found in all areas studied. There were glial filamentous tangles which appeared similar to intranuclear inclusions in astrocytes in all areas studied. Reactive product for mGluR1 was localised only in post-synaptic elements. However, mGluR5 immunoreactivity was demonstrated in both post- and pre-synaptic elements in the molecular layer of the dentate gyrus and CA1 area. Reactive product for mGluR5 was also demonstrated in astrocytes and in the periphery of fibrillary tangles. We postulate that in patients with mesial temporal lobe epilepsy, mGluR1 may increase hippocampal excitability through postsynaptic activation, and mGluR5 may do so through both pre- and post-synaptic mechanisms.

Adolescent↗
PubMed2001

Nitric oxide and subarachnoid hemorrhage: elevated level in cerebrospinal fluid and their implications.

OBJECTIVE: Nitric oxide (NO) plays an important role in the pathogenesis of neuronal injury after brain ischemia, and decreased levels of NO have been implicated in the pathogenesis of vasospasm after subarachnoid hemorrhage (SAH). In this study, we measured the ventricular cerebrospinal fluid (CSF) NO levels in patients with SAH and correlated the levels with clinical grade and middle cerebral artery velocities measured with transcranial Doppler ultrasound. METHODS: All patients with spontaneous SAH documented on computed tomography and with an external ventricular drain inserted within 24 hours of hemorrhage were included in the study. A total of 16 patients were studied between August 1999 and August 2000. CSF was collected serially at the time of surgery and subsequently at daily intervals. It was collected during the time that the external ventricular drain remained patent and in situ. NO levels were measured by photometric analysis by using a nitrite/nitrate assay kit (Cayman Chemical, Ann Arbor, MI). RESULTS: The peak NO level in patients with SAH ranged from 9.96 to 168.16 micromol, with a median of 36.93 micromol. The levels were significantly elevated as compared with the control group (5.16 micromol, P < 0.05). The median NO level in patients with poor-grade SAH was 67.14 micromol as compared with 27.42 micromol in patients with good-grade hemorrhage (P < 0.05). No correlation was seen between CSF NO levels and middle cerebral artery velocities. The median NO level was 33.2 micromol in patients with a poor outcome as compared with 30.25 micromol in patients with a good outcome (P > 0.05). CONCLUSION: This study showed that NO levels are elevated after spontaneous SAH, and the degree of elevation is higher in patients with poor-grade SAH.

Adult↗
PubMed2001

Advances in neurointensive care.

PURPOSE: To highlight recent advances in neurological and neurosurgical intensive care. DATA SOURCES: A MEDLINE search was conducted from January 1980 to August 2000. Keywords included intensive care, head injury, subarachnoid haemorrhage, status epilepticus, myasthenic crisis, Guillain-Barre syndrome and stroke. All articles in English were considered for review. Additional articles were identified from the references of the retrieved articles and cross-referencing selected articles. DATA EXTRACTION: All clinical studies, review articles and abstracts were reviewed. DATA SYNTHESIS: Rapid advances in neurological and neurosurgical intensive care in the last decade have led to the development of specialised neurointensive care units with joint ventures between neurology and neurosurgery. Work in these units have contributed immensely to our understanding of the pathophysiology and management of acute brain injury. The principles of intensive care management include amelioration or reversal of brain injury and preservation of normal neural tissue. Treatment algorithms are possible with the aid of intense clinical and neurophysiologic monitoring. Ongoing clinical and basic science research may provide new treatment options for the intensivist in the acute phase of brain injury. CONCLUSION: Specialised neurointensive care units provide the best environment for the patient with acute brain injury. Outcome is frequently enhanced the clinicians skilled towards dealing with the whole spectrum of neurologic insults.

Critical Care↗
PubMed2000

Nerve growth factor (NGF) loop 4 dimeric mimetics activate ERK and AKT and promote NGF-like neurotrophic effects.

Previous work indicating that nerve growth factor (NGF) protein loops 2 and 4 interact with TrkA receptors raise the possibility that small molecule mimetics corresponding to TrkA-interacting domains that have NGF agonist activity can be developed. We applied our previously developed strategy of dimeric peptidomimetics to address the hypothesis that loop 4 small molecule dimeric mimetics would activate TrkA-related signal transduction and mimic NGF neurotrophic effects in a structure-specific manner. A loop 4 cyclized peptide dimer demonstrated NGF-like neurotrophic activity, whereas peptides with scrambled sequence, added or substituted residues, or cyclized in monomeric form were inactive. Activity was blocked by the TrkA inhibitors K252a and AG879 but not by NGF p75 receptor blocking antibody. Dimeric, but not monomeric, peptides partially blocked NGF activity. This profile was consistent with that of a NGF partial agonist. ERK and AKT phosphorylation was stimulated only by biologically active peptides and was blocked by K252a. The ERK inhibitor U0126 blocked the neurite- but not the survival-promoting activity of both NGF and active peptide. These studies support the proof of concept that small molecule NGF loop 4 mimetics can activate NGF signaling pathways and can mimic death-preventing and neurite-promoting effects of NGF. This finding will guide the rational design of NGF single-domain mimetics and contribute to elucidating NGF signal transduction mechanisms.

Animals↗
PubMed2000

Petrosal approach for a large right posterior cerebral artery (P2) aneurysm.

A seven year old girl presented with recurrent headaches Computed tomography (CT) magnetic resonance imaging (MRI) and angiography showed a 2 cm aneurysm at the P2 segment of the right posterior cerebral artery. The aneurysm was trapped successfully by a petrosal approach. The patient made an excellent recovery except for a transient fourth nerve palsy.

Child↗
PubMed2000

Apoptosis occurs after cerebral contusions in humans.

OBJECTIVE: Animal model systems have shown that head trauma can induce cell death in regions of the brain away from the site of the impact via a process of apoptosis. We sought to determine whether there was evidence of cellular apoptosis in clinically collected materials from human head trauma patients, as well as to attempt to determine the pathway by which it may occur. METHODS: Thirty-one sequential specimens of brain tissue excised during emergency craniotomy for evacuation of cerebral contusions with mass effect were examined. Non-necrotic pericontusional tissues were detected in 11 samples. These were examined for the presence of apoptotic cells by the terminal deoxynucleotide transferase-mediated nick end labeling method as well as by immunohistochemistry to detect possible expression of the apoptosis-related genes p53, bcl-2, and bax. RESULTS: Bax expression was detected in all patients, whereas bcl-2 expression was noted in six patients. Terminal deoxynucleotide transferase-mediated nick end labeling-positive cells were noted in eight patients. One instance of p53-positive immunostaining was observed. Patients with bcl-2 expression had a better survival rate than patients in whom no bcl-2 expression was noted (P = 0.01). CONCLUSION: Although necrosis seemed to be the main finding in cerebral contusions, these results support the hypothesis that apoptosis does occur in patients after traumatic brain injury, and this may contribute to the secondary injury processes that are seen with head injury. Patients in whom anti-apoptotic bcl-2 is induced seem to have a better prognosis. This may have important clinical significance in the development of bcl-2 homologs or bax inhibitors to prevent apoptosis.

Adult↗
PubMed2000

Computer-aided stereotactic functional neurosurgery enhanced by the use of the multiple brain atlas database.

This paper introduces a computer-aided atlas-based functional neurosurgery methodology and describes NeuroPlanner, a software system which supports it. NeuroPlanner provides four groups of functions: 1) data-related for data reading, interpolation, reformatting, and image processing; 2) atlas-related for multiple atlases reading, atlas-to-data global and local registrations, two-way anatomical indexing, and multiple labeling in two and three dimensions; 3) atlas-data exploration-related for three-dimensional (3-D) display and real-time manipulation of cerebral structures, continuous navigation, two-dimensional (2-D), triplanar, 3-D presentations, and 2-D interaction in four views; and 4) neurosurgery-related for targeting, trajectory planning, mensuration, simulating the insertion of microelectrode, and simulating therapeutic lesioning. All operations, excluding atlas and data reading, are real time. The combined anatomical index of the multiple brain atlas database containing complementary 2-D and 3-D atlases has about 1000 structures per hemisphere, and over 400 sulcal patterns. Neurosurgical planning with mutually preregistered multiple brain atlases in all three orthogonal orientations is novel. The approach is validated with 24 intraoperative and postoperative datasets for thalamotomies, thalamic stimulations, pallidotomies, and pallidal stimulations. Its potential benefits include increased accuracy of target definition, reduced time of the surgical procedure by decreasing the number of tracts, facilitated planning of more sophisticated trajectories, lowered cost by reducing the number of microelectrodes used, reduced surgical complications, and the extra degree of confidence given to the neurosurgeon.

Brain Mapping↗
PubMed2000

Downregulation of LAR tyrosine phosphatase prevents apoptosis and augments NGF-induced neurite outgrowth.

The identity of the protein tyrosine phosphatases (PTPs) regulating cell death and responses to neurotrophins during neural development remain unknown. To determine if the leukocyte common antigen-related (LAR) PTP regulates these processes, PC12 cells were made LAR-deficient via stable transfection with an LAR antisense transgene. LAR-deficient cells demonstrated a stable novel phenotype, including a two-fold increase in nerve growth factor- but not fibroblast growth factor-induced neurite outgrowth. Upon serum-deprivation, LAR-deficient cells exhibited a two- to three-fold decrease in cell death. The findings that an endogenous PTP promotes cell death and counter-regulates neurotrophin actions introduce a major new receptor gene family to neurotrophic processes and suggest novel strategies for preventing cell death and augmenting neurotrophin function.

Animals↗
PubMed2000

Stereotactic brain biopsies in AIDS patients--early local experience.

AIM: To assess the usefulness of stereotactic brain biopsies in AIDS patients with cerebral lesions in Singapore. METHODS: A total of 10 patients with AIDS and cerebral lesions underwent stereotactic brain biopsies in the Department of Neurosurgery, Tan Tock Seng Hospital (TTSH) between September 1997 and September 1998. The patients were referred from the Communicable Diseases Centre (CDC), TTSH. These patients either failed a trial of therapy for toxoplasmosis encephalitis (TE) or had CT/MRI scans which did not suggest TE. Four were CT-guided and six were MRI-guided stereotactic biopsies. The Radionics Cosman-Robert-Wells (CRW) stereotactic apparatus was used for all cases. RESULTS: The male to female ratio was 9:1. Histological diagnosis from biopsy was lymphoma (5), metastatic adenocarcinoma (1), TE (1), abscess (1), encephalitis (1) and granulomatous tissue (1-presumed tuberculosis). CONCLUSION: The early experience is that stereotactic brain biopsy is useful in patients with AIDS and cerebral lesions. The etiology is confirmed in the majority of cases and impacts on management decisions and prognostication.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Gene expression along the cerebral-spinal axis after regional gene delivery.

We demonstrate here that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or cationic liposome: DNA complexes (CLDCs) produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Gene expression was identified both within the spinal cord and the brain after intracerebroventricular or intrathecal injection of either CLDCs or plasmid DNA alone. Intracerebroventricular or intrathecal injection of CLDCs containing the beta-galactosidase (beta-Gal) gene produced patchy, widely scattered areas of beta-Gal expression. The chloramphenicol acetyltransferase (CAT) reporter gene product reached peak levels between 24 hr and 1 week postinjection, and was still present at significant levels 3 weeks after a single intracerebroventricular or intrathecal injection. Intrathecal injection of the human granulocyte colony-stimulating factor (G-CSF) gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine nerve growth factor (NGF) gene increased mNGF levels in the hippocampus, a target region for cholinergic neurons in the medial septum, and increased cholinergic neurotransmitter synthetic enzyme choline acetyltransferase (ChAT) activity within the brain, a well-characterized effect of both purified and recombinant NGF protein. These findings indicate that intracerebroventricular or intrathecal injection of CLDCs can produce significant levels of expression of biologically and therapeutically relevant genes within the CNS. Efficient gene transfer into the CNS will facilitate the evaluation of gene function and regulation within the brain and spinal cord. We attempted to transfer and express genes within the brain and spinal cord by direct CNS injection of either DNA alone or CLDCs into the intraventricular and subarachnoid compartments. We show that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or CLDCs produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Intrathecal injection of the hG-CSF gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine NGF gene increased mNGF levels in the hippocampus, and increased cholinergic neurotransmitter synthetic enzyme ChAT activity within the brain. Locoregional diffusion of gene products expressed by transfected meningeal lining cells into brain and spinal cord parenchyma could potentially target secreted proteins within brain and spinal cord regions relevant to neuropathological states while limiting peripheral side effects.

Animals↗
PubMed1999

Extensor pollicis longus paralysis following thoracoscopic sympathectomy.

Thoracoscopic sympathectomy is an acceptable form of treatment for palmar hyperhidrosis. Many authors have reported favourable results. Complications range from pneumo-haemothorax, Horner's syndrome, compensatory hyperhidrosis and bleeding. Plas et al reported 2.7% of the procedures had complications requiring intervention and 9.7% had non-interventive complications. There have been isolated reports of other rare complications including false aneurysm of intercostal artery, inferior brachial plexus injury and abnormal suntanning. We report an unusual case of isolated extensor pollicis longus paralysis after a thoracoscopic sympathectomy for palmar hyperhidrosis, in a fit young male. Such complications have not been previously reported. We recognise that such isolated nerve injury is uncommon.

Adult↗
PubMed1999

An interface for precise and comfortable 3D work with volumetric medical datasets.

We have developed a 3D/2D paradigm of interaction that combines manipulation of precise 3D volumetric data with unambiguous widget interaction. Precise 3D interaction is ensured by a combination of resting the lower arms on an armrest and pivoting the hands around the wrist. Unambiguous 2D interaction is achieved by providing passive haptic feedback by means of a virtual control panel whose position coincides with the physical surfaces encasing the system. We have tested this interface with a neurosurgical planning application that has been clinically used for 17 skull-base cases at two local hospitals.

Computer Simulation↗
PubMed1999

Spontaneous subarachnoid haemorrhage and outcome--results from Tan Tock Seng Hospital, Singapore.

AIM OF STUDY: To ascertain the number of cases of spontaneous (aneurysmal) subarachnoid haemorrhage presenting to Tan Tock Seng Hospital, Singapore, over a one year period, the demographics of the patients involved, their treatment and their eventual outcome. METHOD: A retrospective study from June 1995 to June 1996. RESULTS: There were 62 patients admitted over this period with an average of 5 patients per month. Their ages ranged from 9 to 85 years with a mean of 54 years. All 62 patients underwent 4-vessel cerebral angiograms. Forty-three patients (69%) underwent clipping of their aneurysms. Twelve patients (19%) had negative angiograms. Four patients (6%) underwent coiling of their aneurysms via interventional neuroradiology techniques. Patients with subarachnoid haemorrhage of Grades 1 to 3 on the WFNS (World Federation of Neurological Surgeons) grading had a favourable outcome (Glasgow Outcome Score of 4 and 5) in 85% of the cases. The overall mortality rate for the operated group (all grades) was 11%. However for the group with good WFNS grading, namely the Grade 1 to 2 groups, there were no deaths. Twenty-four percent of patients developed clinically symptomatic vasospasm. Eighteen percent of patients required ventriculo-peritoneal shunting for hydrocephalus secondary to the subarachnoid haemorrhage. The overall management mortality (operated and non-operated cases) was 14% for proven aneurysmal and angiographically-negative spontaneous subarachnoid haemorrhage. These results are comparable to that of other reputable centers reported in the literature.

Adolescent↗
PubMed1999

Decision analytic approach to severe head injury management.

Severe head injury management in the intensive care unit is extremely challenging due to the complex domain, the uncertain intervention efficacies, and the time-critical setting. We adopt a decision analytic approach to automate the management process. We document our experience in building a simplified influence diagram that involves about 3000 numerical parameters. We identify the inherent problems in structuring a model with unclear domain relationships, numerous interacting variables, and real-time multiple inputs. We analyze the effectiveness and limitations of the decision analytic approach and present a set of desiderata for effective knowledge acquisition in this setting. We also propose a semi-qualitative approach to parameter elicitation.

Craniocerebral Trauma↗