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Biomedical subjects

L S Lee

Publications and source records attributed to L S Lee.

At least 37 records · Page 2Linked to original sources

Elevated levels of urine angiostatin and plasminogen/plasmin in cancer patients.

Previously, a specific angiogenesis inhibitor, angiostatin, discovered in urine and serum of tumor-bearing mice, was reported to potently block tumor growth and metastasis in animal models. Detection of angiostatin and its precursor proteins in urine from cancer patients has not been reported. Now, we report the development of an antibody-based analysis system that allows us to detect angiostatin and plasminogen/plasmin (Pgn/plasmin) in the urine of cancer patients. The detection system is a combination of a novel lysine-ELISA assay and Western immunoblot analysis using a specific antibody to human angiostatin and Pgn/plasmin. High levels of Pgn/plasmin were detected in the urine from various cancer patients, whereas healthy individuals showed relatively low levels of urine Pgn/plasmin. Of interest, angiostatin is detectable in urine samples of patients with various cancers, including acute lymphoblastic leukemia, suggesting that angiogenesis may play an important role in the development and progression of leukemia. Our data for the first time show that angiostatin and Pgn/plasmin are present at relatively high levels in the urine of human cancer patients. Detection of urine angiostatin in cancer patients helps us not only to understand the role of this angiogenesis inhibitor in cancer development and progression but also allows us to develop tools of cancer diagnosis and prognosis. Thus angiostatin has both therapeutic and diagnostic implications in cancer disease.

Adolescent↗

Far lateral lumbar disc herniation.

BACKGROUND: Far lateral lumbar disc herniation is an uncommon condition that may compress the nerve root outside the vertebral canal and in its extraforaminal course. The traditional midline interlaminar approach for the exploration of far lateral lumbar disc herniation is often difficult because the intervertebral articulation obviates a direct view of the course of the extraspinal nerve. In this report, we present two surgical approaches for the treatment of far lateral lumbar disc herniation: the paramedian muscle-splitting microtechnique and the enlarged midline approach. METHODS: Eight patients with far lateral lumbar disc herniation were found among 160 lumbar disc operations in 160 patients. According to computed tomography results, we divided patients with far lateral lumbar disc herniations into two groups; the extraforaminal and foraminal groups. Clinical presentation, imaging studies and surgical approach were thoroughly reviewed. RESULTS: Three patients in the extraforaminal group underwent the paramedian muscle-splitting microtechnique. Two patients in the foraminal group underwent the enlarged midline approach. The other three were operated on before the introduction of the paramedian muscle-splitting microtechnique and the enlarged midline approach. One of these patients who underwent the traditional interlaminar approach with resection of the lateral portion of facet joint, received additional instrumentation and fusion for the prevention of further instability. All had good results and no further surgical treatment was necessary. CONCLUSIONS: The incidence of far lateral lumbar disc herniation was 5% of all surgically treated disc herniations at our institution. For the extraforaminal group, the paramedian muscle-splitting microtechnique is the surgical route of choice. For the foraminal group, the enlarged midline approach is better than the traditional, interlaminar approach in saving the facet joint and preventing postoperative instability.

Adult↗

Microsatellite variation and assessment of genetic structure in tea tree (Melaleuca alternifolia-Myrtaceae).

Analysis of five microsatellite loci in 500 Melaleuca alternifolia individuals produced 98 alleles that were useful for population genetic studies. Considerable levels of observed heterozygosity were recorded (HO = 0.724), with approximately 90% of the variability being detected within populations. A low level of selfing (14%) was suggested to be the principal cause of excess homozygosity in a number of populations (overall FIS = 0.073). This study showed low levels of inbreeding in certain populations as well as a significant isolation-by-distance model. Only two groups of populations (Queensland and New South Wales) constituted different genetic provenances as a result of geographical isolation. The M. alternifolia data suggest that microsatellite loci did not always arise by a stepwise mutation process but that larger jumps in allele size may be involved in their evolution.

Australia↗

Bioequivalence study of two morphine extended release formulations after multiple dosing in healthy volunteers.

AIM: Two extended release (ER) formulations of morphine sulphate (30 mg each), Oramorph SR (test) and a marketed reference formulation (MST Mundipharma Retardtabletten), were investigated for their relative bioavailability at steady-state: METHODS: The study was designed as a single-centre, open-label, two-period crossover, pharmacokinetic comparison in 28 healthy male volunteers and was completed in 23 subjects. The determination of morphine and its metabolite morphine-6-glucuronide in plasma was done by HPLC with electrochemical detection after solid-phase extraction. RESULTS: Under steady-state conditions in the first dosing interval, mean maximum plasma concentrations for morphine were 19.1 ng/ml (CV% 41) for Oramorph SR 30 mg and 19.1 ng/ml (CV% 33) for MST-30 Mundipharma Retardtabletten. Geometric mean AUC(0-12) values were calculated as 108 ngxh/ml (CV% 40) for Oramorph SR 30 mg and as 118 ng x h/ml (CV% 30) for the reference formulation. The plasma concentrations of the major metabolite, morphine-6-glucuronide, were found to be generally in a higher range compared to the parent compound. The 90% confidence intervals of test to reference ratios calculated for all relevant parameters (AUC, C(max), PTF) for both the parent compound and morphine-6-glucuronide were all within the limits of 80 - 125%. The most frequent adverse events (AE > 10%) during Oramorph SR 30 mg treatment were headache (36%), dizziness (18%), nausea (21%), vomiting (21%) and pruritus (11%). During treatment with MST-30 Mundipharma Retardtabletten, the most frequent AEs were headache (29%), dizziness (13%), nausea (29%) and vomiting (29%). CONCLUSION: The results demonstrate bioequivalence of Oramorph SR 30 mg and MST-30 Mundipharma Retardtabletten.

Adolescent↗

Pilocytic astrocytoma of the posterior fossa: a follow-up study in 15 patients.

BACKGROUND: The extent of resection in pilocytic astrocytoma of the posterior fossa remains undefined, as the problem of hydrocephalus has not yet been solved. We retrospectively reviewed the data from 15 patients with a pilocytic astrocytoma of the posterior fossa to evaluate the impact of surgical technique, in terms of resection extent, by serial magnetic resonance imaging (MRI) examinations. In addition, the issue of hydrocephalus was considered and related to the different treatment modalities. METHODS: Macroscopic, gross, total resection of the tumor was performed in all 15 patients. Follow-up was obtained in 14 patients for a period ranging between 11 and 119 months (median, 41.5 months). The ages of patients ranged from two to 13 years (mean, 7 +/- 3 years). All patients underwent serial MRI examinations in the first month, every six months for the first two years and then yearly. RESULTS: Outcome was good in 12 patients who had no neurologic deficit and fair in two patients who were slightly handicapped but had an independent life. There were four patients with an abnormally persistent enhancement on MRI, with a median follow-up of 30 months. One of these patients had progressively increasing size of the enhancement. Three of them had the same size of enhancement during the follow-up period. The MRI findings showed residual tumors in four patients. One of them had tumor regrowth one year after surgery. There were 11 cases with pilocytic astrocytoma and hydrocephalus. Five patients were treated with tumor removal and external CSF drainage. Six patients underwent tumor removal only, without perioperative cerebrospinal fluid (CSF) drainage. Only one patient had a permanent ventriculoperitoneal shunt. CONCLUSIONS: Our study illustrated that the extent of tumor resection of pilocytic astrocytoma can be defined by postoperative serial MRI examinations. Long-term follow-up with MRI seems mandatory in cases with abnormal enhancement. Hydrocephalus is a common finding in patients with a pilocytic astrocytoma. A permanent ventriculoperitoneal shunt is required only in patients with postoperative hydrocephalus.

Adolescent↗

Computerized tomography-guided stereotactic aspiration of brain abscesses: experience with 28 cases.

BACKGROUND: Computerized tomography (CT)-guided stereotactic techniques allow accurate identification of brain abscesses and provide promising results for the management of brain abscesses. METHODS: We reviewed the results of stereotactic aspiration of brain abscesses in 28 consecutive patients from 1984 to 1995. In all patients, the diagnosis of brain abscess was made by computerized tomography (CT). All patients underwent stereotactic aspiration of abscesses as the primary surgical therapy. Intravenous antibiotics were administered preoperatively and adjusted according to organism type and sensitivity to antibiotics. In patients with multiple lesions, aspirations were performed on abscesses larger than 2 cm in diameter or on those causing significant mass effects. CT was performed weekly to monitor abscess growth or failure to resolve. Patients were followed on an outpatient basis. This report is a retrospective review of clinical features, diagnostic methods, treatment and postoperative results. RESULTS: A total of 19 patients had good recoveries and six patients had mild neurologic sequelae. One patient had persistent conscious impairment. Intracranial hemorrhage occurred in one patient. Two deaths occurred during hospitalization. One patient with a fungal infection underwent additional surgical excision of the abscess. Most patients had resolution of abscesses after stereotactic treatment within two months. The cure rate was 92% in patients with bacterial brain abscesses treated with stereotactic aspiration and intravenous antibiotics for six weeks. CONCLUSIONS: Stereotactic surgery is a procedure with minimal morbidity and mortality, and can be the treatment of choice for brain abscesses when combined with appropriate antibiotic therapy.

Adult↗

Intraoperative neurosurgical ultrasonography.

BACKGROUND: Ultrasound scanning is a well-established means of evaluating intracranial structures in infants and children with open fontanelles. However, it remains underutilized in neurosurgical operations. We present our experience with the intraoperative use of realtime ultrasonography during 36 neurosurgical procedures. METHODS: Thirty-six intraoperative ultrasonography (IOUS) procedures were performed over the past two years. Thirty-two patients had intracranial lesions and four had intraspinal tumors. A real-time scanner equipped with a 5 MHz and a 7.5 MHz transducer was used during surgery. RESULTS: IOUS worked well, regardless of the location of the craniotomy site. It was useful in localizing and characterizing intracranial and intraspinal masses, assuring the completeness of tumor removal (22 cases), proper positioning of ventricular shunt catheters (5 cases), guiding and confirming the decompression of cysts or abscesses (3 cases) and real time monitoring of surgical complications (36 cases). CONCLUSIONS: IOUS can be helpful in defining intracranial and intraspinal lesions as well as normal architecture. It shortens the operative time and decreases the surgical morbidity. The expertise of the physician with sonographic equipment facilitates its accurate and expedient intraoperative neurosurgical application.

Brain Neoplasms↗

Detection of mammosomatotrophs in paraffin-embedded specimens of various pituitary adenomas.

BACKGROUND: There are various classification systems for pituitary adenomas based on whether mammosomatotroph cells, which simultaneously express both prolactin (PRL) and growth hormone (GH), can be found. Until the present, the identification of such cells required special techniques and could not be performed in paraffin-embedded specimens. This hindered large-scale studies for detection of mammosomatotrophs in various pituitary adenomas and, as a result, such classification has remained controversial. To establish a methodology for the detection of mammosomatotrophs in paraffin-embedded specimens and to propose a more logical classification for pituitary adenomas, the authors conducted this retrospective study. METHODS: We performed double immunofluorescence staining of PRL and GH in paraffin-embedded specimens of various pituitary adenomas with subsequent observation with a confocal laser-scanning microscope. RESULTS: Mammosomatotrophs were found in four of the 10 GH-secreting adenomas and one of the 10 clinically nonfunctioning adenomas. However, mammosomatotrophs were not identified in all 10 cases of prolactinoma. CONCLUSIONS: This is the first report in the literature that successfully demonstrates the presence of mammosomatotrophs in routine paraffin-embedded pituitary adenomas. The new methodology is important for future study of the function and role of these cells. A large-scale study for mammosomatotrophs in various pituitary adenomas with this method and a more logical classification of pituitary adenomas are proposed.

Adenoma↗

Anterior cervical stabilization with the synthes cervical spine locking plate system.

BACKGROUND: The Synthes cervical spine locking plate (CSLP) was originally designed by Mörscher and colleagues, who refined it to prevent the migration and loosening of a locking screw by using a cross-split screw head that could be locked into the plate. This eliminated the requirement of the posterior cortex purchase and thereby decreased the risk of spinal cord injury. The purpose of this report is to review our experience using the cervical spine locking plate system and to evaluate its ability to stabilize the cervical spine. METHODS: Twenty patients with cervical trauma, cervical spondylosis of failed anterior interbody fusion underwent anterior cervical fusion with the Synthes CSLP system between August, 1993, and April, 1996. All patients were evaluated preoperatively and postoperatively by plain radiography and magnetic resonance imaging (MRI). RESULTS: All 20 patients achieved solid bone fusion and 19 of them had neurologic improvement, by a mean follow-up period of 36 months. No patients suffered from neurologic injury as a result of the locking device. No patient demonstrated radiologic evidence of implant failure. The postoperative MRI examination disclosed minimal implant artifacts and adequate spinal cord decompression. CONCLUSIONS: The Synthes CSLP system for anterior stabilization provides efficacy, safety and ease of use. It also caused less distortion and minimal artifacts on postoperative MRI.

Adult↗

Differential inducibilities of GFAP expression, cytostasis and apoptosis in primary cultures of human astrocytic tumours.

Glial fibrillary acidic protein (GFAP) is an astrocytic lineage-specific intermediate filament protein, and its expression or non-expression is inversely correlated with the tumourigenecity of astrocytoma cells. To estimate the GFAP levels of astrocytes in intracranial tumour tissues, we established primary cultures from six astrocytic tumour specimens and used a double-staining flow cytometric method to detect the different levels of GFAP among these primary cultures. Although these primary cultures exhibited the same Matrigel invasiveness, their GFAP expression is inversely related to the rate of cell growth and the histologic grade of the original tumour. Phenylacetate, 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate, which are potent inducers of differentiation in various cancer cells, have been examined for their effects on these primary cultures. Cytostasis was more or less caused by these compounds in all six primary cultures, but induction of GFAP was observed only in the primary culture derived from a less malignant astrocytoma specimen having the highest intrinsic GFAP level. Interestingly, this primary culture, but not others, also exhibited increased HRG-alpha expression after phenylacetate or sodium butyrate treatment. Loss of the inducibility of differentiation-related gene expression could be one of the events involved in the malignant progression of astrocytomas. In addition, the chemotherapeutic agent BiCNU has a killing effect on all six primary culture cells, with LD50 less than 60 nM. The underlying mechanism was through the induction of apoptosis in these primary culture cells regardless of their varying malignancies of original tumours. However, unlike colon cancer and leukaemia cells, sodium butyrate could not induce apoptosis within 4 days in these astrocytic tumour cells, indicating that the cell context of different cell types indeed determined the ability of sodium butyrate to induce apoptosis.

Journal Article↗

Thoracoscopic T2-sympathetic block by clipping--a better and reversible operation for treatment of hyperhidrosis palmaris: experience with 326 cases.

Although thoracoscopic sympathectomy or sympathicotomy is the best treatment for hyperhidrosis palmaris, a new approach of clipping only without transection of T2-sympathetic trunk is just as effective. Aside from the guaranteed cure of hyperhidrosis, this new method has fewer complications and has the advantage of recovery of the sympathetic tone in the hands if the procedure is reversed by the removal of the clips. Between March 18 and September 30 of 1996, 326 patients (190 female and 136 male with a mean age of 20.5 years) underwent thoracoscopic T2-sympathetic block by clipping to treat hyperhidrosis. Good results and few complications were noted during follow up six months to one year postoperatively. Five of the 326 patients, all female, had the operation reversed because of intolerable compensatory sweating. Three recovered from the compensatory sweating within two months and had less palmar sweating than before their sympathetic block; the fourth achieved relief of compensatory sweating after nine months, and the fifth reported no improvement.

Adolescent↗

Single-chain Fv with manifold N-glycans as bifunctional scaffolds for immunomolecules.

Unlike natural antibodies, single-chain Fv (sFv) proteins normally lack asparagine-linked glycosylation. Many designed immunoconjugates and other therapeutics currently employ the advantageous conjugation chemistry or targeting properties provided by the glycoprotein oligosaccharide domain. sFv proteins with engineered N-glycan designs were evaluated in Pichia pastoris for glycosylation efficiency, expression level, oligosaccharide chain length and composition, and affinity. In contrast to nearly all natural glycoproteins, the engineered attachment of N-glycans conveniently near the polypeptide C-terminus was found to produce the optimal results. Furthermore, the percentage modification and chain length of the attached mannose chains were controllable by the use of tandem and overlapping Asn-X-Thr tripeptide sites. The glycosylated sFv mannose chains could be effectively conjugated to polyethylene glycol and the resulting conjugate displayed a 10-fold increased circulating life in mice. The potential to control polymer:sFv or drug:sFv molar ratios by site-specific conjugation may substantially improve the therapeutic efficacy of these minimal antigen-binding molecules.

Animals↗

Protection of visual pathway in gamma knife radiosurgery for craniopharyngiomas.

Craniopharyngiomas present a major challenge to Gamma Knife radiosurgery (GKRS) due to their proximity to the optic apparatus. Based on observations of the evolving tumoral change on MRI and clinical results, an optimization of the treatment strategy and dose selection is possible. From March 1993 to September 1996, 21 patients with craniopharyngiomas were treated by GKRS. Every patient received stereotactic MRI exclusively for targeting and dose planning. The tumor and adjacent structures, including optic nerves, chiasm, and tracts were carefully identified and delineated on sagittal, coronal and axial films. The tumor volume ranged from 0.3 to 28 ml (average 9 ml). We purposefully apply multiple isocenters (average 9.1 shots) to create an isodose curve that covered the tumor optimally while sparing the optic pathway. The marginal dose prescribed was 9.5 to 16 Gy (50%). The maximal dose was 19 to 32 Gy. The maximal dose to the optic apparatus was 3.2 to 12.5 Gy. After GKRS, all patients were followed up clinically every month. MR studies were conducted every six months with the same techniques on the same scanner to investigate evolution of tumor volume and any adverse radiation effect. The follow-up period ranged from 6 to 40 months (mean: 18.4, median: 19). All patients were followed more than 6 months. Nineteen out of 21 cases (90.5%) achieved tumor control; that is, 18 tumor shrinkage (volume reduction: 15-95%) and 1 stabilized tumor growth. Among these 21 patients, 7 had improved visual acuity or visual field after GKRS, and the rest remained stable. Two patients developed mild T2 change on MRI without any endocrinological disturbance or visual impairment. Protection of the visual pathway can be secured by a sophisticated delineation on 3-dimensional stereotactic images with multiple-shot dose planning. Craniopharyngiomas with tumor volume up to 25 ml were treated safely and effectively, because the dose to the optic apparatus was kept as low as possiby this strategy. Further follow-up is needed to determine the highest tolerable dose to surrounding critical structures and the long-term outcome of tumor control.

Adolescent↗

Aneurysmal subarachnoid hemorrhage in Taiwan.

In 1993, the annual report about prospective survey and registry of stroke revealed there were 439 cases of ruptured intracranial aneurysms in Taiwan area. Thirty-two of them had multiple aneurysms; therefore, totally 476 aneurysms occurred in these cases. The anatomic distribution of these aneurysms were as the following: internal carotid artery-posterior communicating artery 32%, anterior communicating artery 30%, middle cerebral artery 18%, carotid bifurcation 6%, anterior cerebral artery 4%, carotid-ophthalmic artery 2%, intracavernous carotid artery 2%, and vertebrobasilar system 6%. 364 cases received surgical or interventional treatment, which 88% was clipping procedure, 8% was interventional procedure with coil, and 4% was wrapping. The surgical mortality was 13%.

Humans↗

Assessment of protein conformation in human benign and malignant astrocytomas by reflectance Fourier transform infrared microspectroscopy.

The secondary structure and composition of protein in the tissues of benign and malignant astrocytomas were determined by reflectance Fourier-transform infrared (FT-IR) microspectroscopy. The peak maximum of IR spectra of the tissues from recurrent malignant astrocytoma markedly appeared at higher frequency (1655 or 1663 cm(-1)), which was significantly different from that of the tissues from benign astrocytoma at 1651 cm(-1) and tissues from malignant astrocytoma at 1652 cm(-1). Malignant astrocytoma indicated slightly different compositions in the protein secondary structure from benign astrocytoma. However, a significant increase in beta-turn structure but a marked decrease in beta-sheet and random coil structures were observed in the protein secondary structure of the recurrent malignant astrocytoma. The phenomenon was more pronounced in recurrent malignant astrocytoma pretreated with radiation and chemotherapy. The rapid cell proliferation and cell differentiation of malignant astrocytoma with or without recurrence might be the possible explanations for the different compositions of protein conformational structures.

Adult↗

The haemodynamic effect of thoracoscopic cardiac sympathectomy.

A patient with angina pectoris who had been successfully treated by thoracoscopic cardiac sympathectomy was scheduled to have scalp debridement under general anaesthesia for a scald burn. There were haemodynamic changes during and after the operation including anaesthetic induction, endotracheal intubation, maintenance, and early recovery period. The sympathetic denervated heart showed little chronotropic response to anaesthetic and surgical stimulation. On the contrary, the parasympathetic response was predominant. An episode of severe bradycardia occurred during endotracheal suctioning prior to extubation. The haemodynamic response to cardiac sympathetic denervation corresponded to the efferent effect of beta-receptor blockade

Aged↗

Effects of gamma knife radiosurgery for brain tumors: clinical evaluation.

BACKGROUND: Gamma knife radiosurgery is a safe and effective alternative to microsurgery in the management of selected intracranial lesions. In our initial three-year experience with gamma knife radiosurgery, 431 patients were treated using this method. This report presents the treatment results for three different types of brain tumors: benign meningiomas, malignant metastases and gliomas. METHODS: A retrospective study was performed to analyze a consecutive series of 71 meningiomas, 31 metastatic tumors and 21 gliomas treated by gamma knife radiosurgery between March 1993 and May 1996. The treatment results were investigated using regular magnetic resonance examinations and tumor volume measurement at six-month intervals to observe sequential changes of the tumors. Patients with meningiomas were further divided into three groups according to the peripheral radiation doses: high-dose (20-17 Gy, n = 18), medium-dose (16-15 Gy, n = 33) and low-dose (14-12 Gy, n = 20). The Generalized Estimation Equation was applied to compare treatment results in these three groups with different doses and tumor volumes. RESULTS: Volume measurements of the 71 meningiomas showed that 76% decreased in size, 16% stabilized and 8% increased in size. The volumes increased most frequently in the early stage (6-12 months) after treatment and subsequently regressed after the twelfth month. The tumor control rate for meningiomas in our three-year follow-up was over 90%. For meningiomas, the statistical analysis showed that both the radiation dose and tumor volume were significantly related to the development of adverse radiation effects (p < 0.05). In metastatic tumors, rapid tumor regression after radiosurgery was found in 87% of the patients. In gliomas, radiosurgery effectively inhibited tumor growth in selected patients with small, circumscribed, less infiltrative tumors. Ependymomas and low-grade astrocytomas had more favorable outcomes than other gliomas. CONCLUSIONS: Gamma knife radiosurgery is effective for controlling tumor growth in benign meningiomas for up to three years after surgery. In selected cases of malignant metastasis and gliomas, most patients appeared to benefit from the treatment with symptomatic improvement and prolonged survival. Treatment strategy and dose selection in radiosurgery should be adjusted to optimize tumor control and avoid adverse radiation effects.

Brain Neoplasms↗

Multiple bilateral thoracic meningoceles without neurofibromatosis: a case report.

Lateral thoracic meningoceles are rare and, in most cases, they are associated with neurofibromatosis. We report a case in which computerized tomography (CT)-myelography established the diagnosis of multiple, bilateral, lateral, thoracic meningoceles without neurofibromatosis. Plain film radiographs are necessary to evaluate any associated kyphoscoliosis and its progression. CT and magnetic resonance imaging demonstrate the extent of bony erosion, and the size and number of lateral thoracic meningoceles. CT-myelography reveals contrast medium in the meningoceles and is the major diagnostic imaging modality.

Humans↗