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Biomedical subjects

A L Kwan

Publications and source records attributed to A L Kwan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Outcome of spontaneous subarachnoid hemorrhage of unknown etiology.

During a 7-year period, 56 patients with a verified subarachnoid hemorrhage (SAH) in whom neuroradiological investigations failed to reveal a reasonable cause of the bleeding were evaluated. Forty-six patients who survived the SAH were interviewed at a follow-up examination from 10 to 82 months (mean 37 months) after the bleeding. Early prognosis of an unfavorable outcome was possible on the basis of two clinical variables: the poor Glasgow coma scale (GCS < = 11) at admission and the Fisher's SAH grade of greater than II on brain computerized tomographic scans. Other clinical variables in the acute stage, including age, sex, a history of hypertension and the complications of SAH, such as vasospasm, hydrocephalus, and rebleeding, were not related to the early outcome. GCS on discharge was predictive of activity of daily life at follow-up review. On the follow-up, 80% of the patients experienced a good recovery. Rebleeding episode occurred in a patient 5 years after the bleeding. The overall rebleeding rate was 2.2% (equivalent to an annual recurrence of 0.7%). This study confirmed a good prognosis for patients with SAH of unknown cause. We recommend that after thorough panangiography, those patients with SAH of unknown etiology should be encouraged to return to a normal life style without any restriction.

Activities of Daily Living↗
PubMed1997

Attenuation of vasospasm and hemoglobin-induced constriction in the rabbit basilar artery by a novel protease inhibitor.

Calcium-activated proteolysis mediated by the protease inhibitor, calpain, has recently been implicated in the pathogenesis of cerebral vasospasm. The effect of one inhibitor of calcium-activated proteolysis, z-Leu-Phe-CONH-morpholene (zLF), on cerebrovascular constriction was examined in two experimental paradigms. In the first paradigm, the rabbit basilar artery (BA) was visualized via a transclival exposure, and its diameter was monitored using videomicroscopy. In the second experimental paradigm two intracisternal injections of autologous blood were administered to mimic a subarachnoid hemorrhage (SAH). The BA was visualized via the transclival exposure, and its luminal diameter was measured. Topical application of oxyhemoglobin (OxyHb), a known pathogenic agent in cerebral vasospasm, elicited vasoconstriction in normal animals, reducing arterial diameter to approximately 75% of resting levels. Pretreatment with zLF (100, 200, or 300 microM) attenuated vasoconstriction induced by OxyHb. In an experimental model of SAH, the diameter of the BA was reduced after the first injection of blood to approximately 67% of normal resting levels when measured 3 to 4 days later. This vasospastic response was reversed significantly by topical application of zLF (100 microM); vascular diameter was increased to approximately 84% of normal resting levels. These findings demonstrate that both acute OxyHb-induced constriction and blood-induced vasospasm are sensitive to an inhibitor of the proteolytic enzyme, calpain. Together, these observations indicate an important role for calcium-activated proteolysis in the development and maintenance of vasospasm after SAH. In addition, it may be inferred from the data that inhibitors of calcium-activated proteolysis may be useful therapeutic agents for treating this form of cerebrovascular disease.

Journal Article↗
PubMed1997

Inhibition of nitric oxide generation and lipid peroxidation attenuates hemolysate-induced injury to cerebrovascular endothelium.

The mechanisms of hemolysate-induced cerebral injury following subarachnoid hemorrhage are just beginning to be clarified. This study examined the injurious effects of hemolysate on endothelial cells derived from bovine middle cerebral arteries, and evaluated the roles of lipid peroxidation and nitric oxide production in this type of damage. Cultured endothelial cells were grown to confluency on gelatin-coated plates. The cells were characterized as endothelial cells on the basis of morphology. Factor VIII-related antigen staining, and low density lipoprotein (LDL) uptake. Additional cells were grown to confluency on collagen-coated well inserts, and were treated with hemolysate for 24 hours. Prior to hemolysate exposure, cells were treated with: a) an inhibitor of iron-dependent lipid peroxidation (tirilazad mesylate 100 microM), or b) an inhibitor of nitric oxide synthase (either N-nitro-L-arginine: NLA 300 microM, or aminoguanidine: AG at 1.5, 7.5, 15 or 150 microM). Permeability of the tracer, U-14C-sucrose, across the layer of endothelial cells was examined over a 24 hour period. Hemolysate induced a significant increase in the permeability across the endothelial cell layer. Pretreatment with tirilazad mesylate, NLA, or AG attenuated significantly hemolysate-induced changes in the endothelial cell barrier. These findings indicate that free radical generation and lipid peroxidation are critical participants in hemolysate-induced injury to the barrier function of the cerebrovascular endothelium. In addition, the results indicate that endothelial cells provide an adequate source of nitric oxide to damage their own cellular function. Finally, these findings strongly implicate free radical mechanisms in endothelial damage associated with subarachnoid hemorrhage.

Animals↗
PubMed1997

Differential hydroxylation of salicylate in core and penumbra regions during focal reversible cerebral ischemia.

BACKGROUND AND PURPOSE: Free radical-mediated damage during and/or after cerebral ischemia is thought to participate in the elaboration of stroke-related injury. To elucidate the role of this mechanism in cerebral damage, the study presented herein sought to clarify the spatial and temporal features of the free radical response to transient ischemia. With use of a reproducible model of in vivo focal ischemia/reperfusion, the time course of salicylate hydroxylation was measured in ischemic core and penumbra regions. METHODS: Transient focal cerebral ischemia was produced in Sprague-Dawley rats by occluding both carotid arteries and one middle cerebral artery for 3 hours, followed by reperfusion. Cerebral reperfusion was confirmed by visual inspection and iodo[14C]antipyrine autoradiography. A microdialysis probe was placed stereotactically in either the ischemic core or ischemic penumbra of the frontoparietal cortex; the probe was perfused with salicylate, and dialysate samples were analyzed by high-performance liquid chromatography for salicylate hydroxylation products. RESULTS: Salicylate hydroxylation was significantly increased during ischemia and was further increased during 6 hours of reperfusion in the penumbra compared with sham controls. In comparison, a delayed increase in hydroxylation was observed within the ischemic core region only after 3 hours of reperfusion. CONCLUSION: A differential generation of salicylate hydroxylation occurs in core and penumbra regions in association with focal ischemia/reperfusion of the rat neocortex. The early and progressive response in the penumbra suggests that free radical mechanisms may be continuously active in the aggravation of injury in the ischemic penumbra during ischemia and reperfusion. In contrast, the relatively delayed onset of hydroxylation in the core region indicates that this mechanism participates primarily in the late stages of ischemic injury in densely ischemic tissue. These findings are consistent with the concept that the role of free radicals in cerebral injury may differ qualitatively and/or quantitatively in areas of total and partial cerebral perfusion.

Animals↗
PubMed1997

Prevention and reversal of cerebral vasospasm by an endothelin-converting enzyme inhibitor, CGS 26303, in an experimental model of subarachnoid hemorrhage.

Delayed cerebral ischemia due to cerebral vasospasm is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (SAH). Increasing evidence implicates the potent vasoconstrictor peptide endothelin (ET) in the pathophysiology of cerebral vasospasm. In the present study the authors examined the therapeutic value of blocking the production of ET-1 by inhibiting the conversion of its relatively inactive precursor, Big ET-1, to a physiologically active form. An inhibitor of ET-converting enzyme (ECE), CGS 26303, was injected intravenously after inducing SAH in New Zealand white rabbits. Injections of CGS 26303 were initiated either 1 hour after SAH (prevention protocol) or 24 hours after SAH (reversal protocol). One of three concentrations (3, 10, or 30 mg/kg) of CGS 26303 was injected twice daily, and all animals were killed by perfusion fixation 48 hours after SAH occurred. Basilar arteries were removed and sectioned, and their cross-sectional areas were measured in a blind manner by using computer-assisted videomicroscopy. Treatment with CGS 26303 attenuated arterial narrowing after SAH in both the prevention and reversal protocols. The protective effect of CGS 26303 achieved statistical significance at all dosages in the prevention protocol and at 30 mg/kg in the reversal protocol. These findings demonstrate that inhibiting the conversion of Big ET-1 to ET-1 via intravenous administration of an ECE inhibitor can be an effective strategy for limiting angiographic vasospasm after SAH. Moreover, the results demonstrate that treatment with the ECE inhibitor is capable of reducing vasospasm even when initiated after the process of arterial narrowing has begun. Finally, the results provide further support for the role of ET in the establishment of cerebral vasospasm. The ECE inhibitor CGS 26303 thus represents a promising therapeutic agent for the treatment of cerebral vasospasm following aneurysmal SAH.

Animals↗
PubMed1997

Hemolysate induces structural and functional injury to cultured cerebral endothelial cells.

Damage to the vascular endothelium is considered an important feature in the development of cerebral vasospasm following subarachnoid hemorrhage. The present study examined this issue by testing the effects of hemolysate on the morphology and barrier function of cultured Bovine Middle Cerebral Artery Endothelial Cells (BMCA-ECs). Hemolysate elicited a dose-dependent loss of cells in confluent cultures of BMCA-ECs. The shape of the surviving cells changed from a typical cobblestone appearance to a spindle-like appearance with increased vacuolization. Hemolysate-induced damage was reduced by co-incubation with bovine calf serum (BCS) in a concentration-dependent manner. The early impact of hemolysate on endothelial cells was evaluated using a permeability assay in which the passage of 14C-sucrose across a BMCA-EC monolayer was analyzed. Hemolysate significantly increased the permeability of 14C-sucrose across the endothelial barrier. In contrast to its protective effects against cell loss, BCS did not block the early hemolysate-induced increase in transcellular permeability. These findings further implicate erythrocyte contents in the pathogenesis of structural and functional damage to the endothelium following subarachnoid hemorrhage.

Animals↗
PubMed1996

Systemic administration of an inhibitor of endothelin-converting enzyme for attenuation of cerebral vasospasm following experimental subarachnoid hemorrhage.

The potent vasoconstrictor peptide, endothelin-1 (ET-1), has been implicated in the pathophysiology of cerebral vasospasm that occurs after subarachnoid hemorrhage (SAH). This peptide is synthesized as a large prepropeptide that requires a series of modifying steps for its activation. The last of these steps involves the proteolytic conversion of a relatively inactive propeptide, Big ET-1, to its active, 21-amino acid peptide form. The enzyme responsible for converting Big ET-1 to ET-1 is a metalloprotease called endothelin-converting enzyme (ECE). In the present study the authors examined the effects of a newly developed inhibitor of ECE on responses to ET peptides in the normal basilar artery and on pathophysiological constriction in the spastic basilar artery after SAH. In the first series of experiments the authors examined normal basilar arteries in the rabbit, which were exposed transclivally and measured on-line using videomicroscopy. Intravenous administration or topical application of an active inhibitor of ECE, CGS 26303, blocked vasoconstrictor responses to topically applied Big ET-1 but not to ET-1. In contrast, topical application of a structurally related compound that does not inhibit ECE, CGS 24592, was ineffective in blocking vasoconstriction that was elicited by a topical application of Big ET-1. These findings indicate that CGS 26303 when administered systemically is capable of blocking the conversion of Big ET-1 to ET-1 in the basilar artery without affecting the ability of the vessel to respond to ET-1. In the second series of experiments the authors examined the effects of the ECE inhibitor on cerebral vasospasm after experimental SAH. Intraperitoneal administration of CGS 26303 via osmotic minipumps significantly attenuated the delayed spastic response of the basilar artery to an intracisternal injection of autologous blood. This study provides the first evidence that systemic administration of an inhibitor of ECE is capable of preventing cerebral vasospasm after SAH. The results reinforce a growing body of evidence that ETs play a critical role in the development of spastic constriction after SAH. Moreover, the findings indicate that blocking the conversion of Big ET-1 to its active ET-1 form using CGS 26303 may represent a feasible strategy for ameliorating cerebral vasospasm.

Animals↗
PubMed1996

Mechanisms of [Ca++]i elevation induced by erythrocyte components in endothelial cells.

Erythrocyte components released from blood clot after subarachnoid hemorrhage are thought to be involved in the pathogenesis of cerebral vasospasm. The effect of erythrocyte components on smooth muscle has been investigated extensively; however, their action on endothelium remains unclear. We studied the effects of different erythrocyte components and bloody cerebrospinal fluid (CSF) on [CA++]i in cultured bovine pulmonary and cerebral arterial endothelial cells using fura-2 [Ca++]i microfluorimetry. Erythrocyte lysate and bloody CSF produced a biphasic [Ca++]i response, a peak and a plateau, and the effect of erythrocyte lysate on [Ca++]i was attenuated by the endoplasmic reticulum Ca++ pump inhibitors thapsigargin and cyclopiazonic acid, by the voltage-independent Ca++ channel blocker SK&F96365, by the P450 cytochrome inhibitors econazole and miconazole and by the inorganic Ca++ pathway blockers lanthanum, nickel and cobalt. This suggests that erythrocyte lysate releases Ca++ from internal stores and promotes Ca++ influx from voltage from voltage-independent Ca++ channel. Erythrocyte lysate was then fractionated into different molecular weight fractions with different pore-size membranes and each fraction was tested separately. The component that increased [Ca++]i had a molecular weight < 1 kdalton. Fractions that contained oxyhemoglobin did not affect [Ca++]i. Adenosine nucleotides mimicked the effect of erythrocyte lysate and bloody CSF on [Ca++]i. The P2-purinoceptor antagonist suramin attenuated the effect of ATP, erythrocyte lysate, the fraction < 1 kdalton and bloody CSF. We concluded that adenosine nucleotides are the component of erythrocyte lysate and bloody CSF that increase [Ca+2]i in endothelial cells and that the effect involves P2-purinoceptors. However, no evidence is presented that this increase in endothelial [Ca+2]i by erythrocyte lysate causes cerebral vasospasm.

Adenosine↗
PubMed1996

Brain metastasis from pericardial angiosarcoma.

A case of metastatic intracranial angiosarcoma in a 17-year-old female is presented. The patient underwent a sternotomy for treatment of a primary angiosarcoma arising from the pericardium. The postoperative course was uneventful but the patient died as a result of multiple metastases. The metastatic intracranial tumor had features characteristic of angiosarcoma as revealed by light microscopy with positive immunohistochemical staining of factor VIII-related antigen. Only a few cases of intracranial metastasis from cardiac angiosarcoma have been reported in the literature.

Adolescent↗
PubMed1995

Yolk sac tumor of unknown origin with intracranial and spinal metastases.

Primary intracranial yolk sac tumor (Endodermal sinus tumor, YST) is quite rare, and most usually involves the pineal gland. This report concerns a rare case of unknown origin of yolk sac tumor with intracranial and spinal metastases. The 6-year-old boy initially manifested symptoms of acute urinary retension and paraparesis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed an intrathecal tumor spreading below the third lumbar segment, and tumors also appeared in the left temporal area and right cerebellar hemisphere. The pineal region was free of neoplastic involvement and the gonads were normal. The patients underwent operation to remove intracranial and spinal tumors, and postoperative radiotherapy was administered. The histological findings showed metastatic yolk sac tumor. Multiple intracranial and spinal seeding were noticed postoperatively. The patient died of recurrent YST and pneumonia three months after operation. The origin of secondary YST can always be found in specific midline sites. This is a rare case since the primary lesion is unknown.

Brain Neoplasms↗
PubMed1995

[Intracranial aneurysm in Taiwan].

We reviewed the epidemiologic and clinical features of ruptured intracranial aneurysms based on the available data in the literature reported in Taiwan. Among 28,763 stroke patients registered by members of the Neurological Society of Taiwan, 600 patients had verified intracranial aneurysms (2.1%), constituting only 34.7% of 1,730 patients with subarachnoid hemorrhage. The male to female ratio was 0.68.1. The mean age was 54.6 +/ 14.3 years in men, and 56.5 +/ 13.8 years in women. Among the 409 patients whose aneurysmal sites were recorded, the aneurysm occurred at the anterior communicating artery in 109 (26.7%), at the posterior communicating artery in 90 (22.0%), at the internal carotid artery in 82 (20.1%), at the middle cerebral artery in 80 (19.6%), at the anterior cerebral artery in 50 (12.2%), at the vertebral-basilar system in 13 (3.2%), and multiple sites in 33 (8.1%). Cerebral angiography was performed in 72.2% of patients and operation was undergone in 57.7%. A randomized follow-up study in 59 patients showed survival rates of 63% for 1 month, 53.3% for 6 months and 43.6% for 1 year. The reported surgical mortality rates ranged from 7.7% to 12.5%. Prognosis was related to the score on the World Federation of Neurological Societies Subarachnoid Hemorrhage Scale. In Taiwan, the number of patients with intracranial aneurysm has been underestimated among who have presented with subarachnoid hemorrhage. The high mortality and morbidity of aneurysm rupture justify an aggressive attempt to establish a prompt and accurate diagnosis.

Adolescent↗
PubMed1994

[Birth weight percentiles of premature infants needs to be updated].

OBJECTIVE: To analyse whether the conventional so-called Kloosterman charts for birthweight of preterm infants based on data from 1931-1965 are still valid. DESIGN: Descriptive investigation. LOCATION: The Netherlands. METHOD: Data were obtained from the 'project of the premature and small for gestational age' (POPS) survey in 1983. The population consisted of 855 Caucasian infants born after a pregnancy of 24-31 weeks. RESULTS: In nearly all gestational age categories the percentages of small-for-gestational age infants were higher than the 10% they should have been by definition; the percentages of large-for-gestational age infants were much lower than 10%. After exclusion of elective births the percentages remained different. CONCLUSION: These shifts in the birthweight distribution are probably the result of changes in obstetrics. The birthweight percentiles for preterm births will have to be updated.

Birth Weight↗
PubMed1993

Bilateral simultaneous hypertensive intracerebral hemorrhages.

Bilateral simultaneous hypertensive intracerebral hemorrhages (HICH) are a rare occurrence. Computed tomography (CT) enables us to diagnose such a condition which is difficult to recognize clinically. In the series, six patients (2.6%) from a series of 553 HICH cases had suffered from simultaneous rehemorrhage in the contralateral hemisphere. It comprised four males and two females. Their ages ranged from 54 to 64 years with a mean age of 58 years. The clinical symptoms were excessively sever and were characterized by severe consciousness disturbance (semicoma to coma, 6 cases), aphasia (5 cases) and bilateral paresis (3 cases). CT density profiles were identical, implying that the hematomas were of similar age but located areas; two were bilateral basal ganglia, one was bilateral specular thalamus, pontine-ganglia (right), thalamo (left)-ganglia (right) and occipito (right)-thalamus (left) individually. All of the hematomas had ruptured into the ventricles. The predominant sites of hemorrhage were in the putamen (50%, 6/12) and the thalamus (33%, 4/12). Two patients received emergency craniotomy for evacuation of the hematomas. However, they died soon after the operations. In the remaining four non-surgical cases, two died of central failure, another died of pneumonia and the remain one survived but retained hemiplegia sequelae. The serious surgical results and outcome in bilateral HICH was compared that of unilateral HICH. Hemodynamically, poor cerebral blood flow and diaschisis phenomenon may contribute to the poor prognosis in these patients.

Cerebral Hemorrhage↗
PubMed1992

Cystic intracranial meningioma.

Between April 1983 and April 1991, we studied nine cases of intracranial meningioma with cystic change out of 100 intracranial meningioma patients. The incidence was 9%. The patient's ages ranged from 40 years to 75 years old. There were five men and four women, of them, three had intratumoral cysts, and six had peritumoral cysts. Histologically, 7 cases were diagnosed as meningothelimatous type, one as psammomatous and the other one as angioblastic type. All the tumors with cystic change in this series were greater than two centimeters in diameter. Because the morphology was indistinct, Nauta's type II cystic meningioma was easily misdiagnosed as glioma or metastatic tumors preoperatively. Microsurgery is the best way for complete removal of the cyst wall to prevent recurrence.

Adult↗
PubMed1992

The significance of immunosuppression and hormonal alteration in neurotraumatology.

Thirty head trauma patients receiving no steroid treatment were investigated for a period of 20 days. The patients were divided into three groups according to their Glasgow Coma Scale (GCS) scores: GCS = 4-8 and GCS = 9-13. We studied their immunological and hormonal status with special reference to the relationship among severity of trauma, immunosuppression and hormonal alteration. The immunity tests included lymphocyte transformation, lymphocyte phenotyping and delayed hypersensitivity (DH) skin tests. The hormone study consisted of serum cortisol and ACTH level determinations. The following results were obtained: (1) The entire group suffered from significant suppression in lymphocyte responses to mitogens PHA and Con A on day 1 and day 10 after injury, but later they improved; (2) There was a significant fall (P less than 0.05) in OKT3 OKT4 and active T-cell on day 10, especially in patients with GCS less than or equal to 8; (3) A significant increase in OKT8 and decrease in OKT4 was concurrently noted causing an inversion in the ratio of OKT4 to OKT8 on the 10th day (patients 0.96:1, normal 1.6:1, P less than 0.01); (4) No significant change was observed in the number of B-cells, suggesting that cell-mediated immunity may be affected earlier and more severely than antibody producing capacity; (5) Delayed hypersensitivity skin test showed a high incidence of anergy in the severe (GCS less than or equal to 8) and fetal cases. A high mortality in anergic cases was also noted; (6) Elevated ACTH and cortisol levels detected upon arrival rapidly declined to normal value at day 5. In addition, we found no correlation between the curve of serum ACTH and cortisol alteration and the biphasic suppression curve of lymphocyte transformation in later study period. These findings suggest that the severity of natural resistance impairment seems to be related to the gravity of clinical manifestations and to the serum hormonal alteration only in the initial stages. Also, we find that the development of anergy may be an index of poor prognosis.

Adrenocorticotropic Hormone↗
PubMed1992

Intracranial meningioma.

Eighty-three patients with intracranial meningioma were retrospectively analyzed with regard to age, sex, anatomic location, mode of presentation and surgical outcome. The ages of the patients ranged from 11 to 77 years. Fifty-five (66%) were females and 28 (34%) were males. The peak incidence occurred between 40 and 49 years. The locations of the meningioma were as follows: 42.2% in the convexity, 15.7% in the parasagittal, 12.1% in the tuberculum sellae, 8.4% in the sphenoid ridge, and three cases with multiple lesions. Forty-two percent of our series were found to have hyperostosis of the skull bone. There were 7 cases with cyst formations found through computed tomography (CT). Histological classification showed 48.3% to be of meningothelimatous type, while 18.4% were of psammomatous type. One of the multiple meningiomas showed two different histological types. The degree of perifocal brain edema at CT scan was found to be related to the symptoms, the size of the tumor and seizure attack. Fifty-three out of 54 patients with episodes of seizures were found to have perifocal brain edema, whereas the histological features were less significant. Seventy-one tumors were treated by total resection and 16 tumors by subtotal resection. Follow-up study from 1 to 7 years showed the rate of recurrence in the total resection group to be 11.3%; in the subtotal resection group without radiation 42.9%, and in the subtotal resection group with radiation 66.7%. The over-all recurrence rate was 19.5% in our series.

Adolescent↗
PubMed1990

Multiple meningiomas: two cases report.

Two female patients were confirmed to have multiple meningiomas after presenting with different symptoms and signs. Brain computed tomogram (CT) showed multiple homogeneous high contrast uptake in both cerebral hemispheres mimicking that of a glial or metastatic tumor in one case and intracerebral hemorrhage in the other.

Brain Neoplasms↗