Biomedical subjects

Chih-Lung Lin

Publications and source records attributed to Chih-Lung Lin.

8 recordsLinked to original sources

PubMed2003

A murine model of subarachnoid hemorrhage-induced cerebral vasospasm.

Cerebral vasospasm remains a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). The availability of a mouse model of SAH that is simple, replicable and has low mortality would provide a powerful approach for understanding cellular and molecular mechanisms contributing to post-SAH pathologies. The present study characterizes a mouse model of experimental SAH, which produces consistent constriction of large cerebral arteries. Adult mice received injections of autologous blood into the cisterna magna, and the diameters of large intracranial vessels were measured 1 h to 7 days post-SAH. A diffuse blood clot was evident in both the anterior and posterior circulations after SAH. Vascular wall thickening, lumenal narrowing and corrugation of the internal elastic lamina were observed. Both acute (6-12 h) and delayed (1-3 days) phases of vasoconstriction occurred after SAH. Overall mortality was only 3%. A reproducible, low mortality model of SAH-induced cerebral vasospasm in mice is described. This mouse model should facilitate the delineation of cellular and molecular mechanisms of SAH-induced pathologies because of the widespread availability of various technologies for this species (e.g. genetically-altered animals and gene expression arrays). This model also represents a replicable and inexpensive approach for screening therapeutic candidates.

Animals↗

PubMed2003

High cervical midline punctate myelotomy in the management of visceral pain in the mouse.

Increasing evidence implies the existence of a visceral pain pathway in the dorsal column of the spinal cord. Limited midline myelotomy has been used to treat intractable pelvic cancer pain. However, no obvious evidence has been provided that high cervical punctate midline myelotomy (CPMM) relieves visceral pain originating from the abdomen. This study was designed to examine the pain relief effect of CPMM in a mouse model of visceral pain. Thirty-six Institute of Cancer Research (ICR) mice were divided into three groups: Group 1, healthy controls; Group 2, treated with CPMM at C1 and C2; and Group 3, a sham group that underwent laminectomy at C1 and C2 without CPMM. All animals were tested for antinociception in the writhing test 24 hours after surgery. Visceral pain-related behaviors were counted from 5-20 minutes after intraperitoneal injection of 0.6% acetic acid. Writhing test scores were not significantly different between Groups 1 (56.7 +/- 10.7) and 3 (50.7 +/- 17.4). However, Group 2 (30.0 +/- 14.3) showed more than 40% antinociception after treatment, and writhing test scores were significantly different from those of Groups 1 and 3 (p < 0.001). Our results confirm that midline punctate myelotomy can relieve visceral pain and imply that there is a pathway in the posterior funiculus that signals visceral pain. Punctate midline myelotomy at the cervical or high thoracic level may be an alternative strategy in the management of intractable visceral pain due to abdominal or pelvic cancers.

Animals↗

PubMed2002

Attenuation of SAH-induced cerebral vasospasm by a selective ECE inhibitor.

CGS 26303, a dual inhibitor of endothelin-converting enzyme-1 (ECE-1) and neutral endopeptidase 24.11, was previously shown to prevent and reverse vasospasm in an experimental model of subarachnoid hemorrhage (SAH). However, reversal of the vasospastic response was not very efficacious. This study was designed to examine the effects of a highly selective ECE-1 inhibitor, CGS 35066, on SAH-induced cerbrovasospasm. Experimental SAH was induced in New Zealand white rabbits by injecting autogenous blood into cisterna magna and CGS 35066 was injected i.v. twice daily, either at 1 h (prevention protocol) or 24 h (reversal protocol) after SAH. Treatment with CGS 35066 significantly attenuated basilar arterial narrowing at a dose of 1 mg/kg in both protocols. These findings provide support for the use of selective ECE-1 inhibitors for the treatment of SAH-induced vasospasm even after the process of arterial narrowing has begun.

Animals↗

PubMed2002

Oral administration of an inhibitor of endothelin-converting enzyme attenuates cerebral vasospasm following experimental subarachnoid haemorrhage in rabbits.

Increasing evidence has implicated endothelin-1 (ET-1), a potent vasoconstrictive peptide, in the pathophysiology of cerebral vasospasm after subarachnoid haemorrhage (SAH). Endothelin-converting enzyme-1 (ECE-1), the protease involved in the final step of post-translational processing of ET-1, cleaves the inactive precursor big ET-1 at the Trp(21)-Val (22) peptide bond. In our previous study, we found that an inhibitor of ECE-1, CGS 26303, could prevent and reverse the arterial narrowing after SAH in rabbits. CGS 26393, a prodrug of CGS 26303, is an orally active, long-acting inhibitor of ECE-1. The present study examined the effects of CGS 26393 on the prevention and reversal of cerebral vasospasm after SAH. New Zealand white rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. In the prevention study, the drug was given orally 1 h before the induction of SAH. All drug treatments in the reversal study were initiated at 23 h after induction of SAH. One of three dosages (3, 10 or 30 mg/kg) of CGS 26393 or vehicle was administrated orally twice daily, and all animals were sacrificed by perfusion and fixation 48 h after SAH. Basilar arteries were removed and sectioned, and cross-sectional areas were measured. Cerebrospinal fluid (CSF) was collected prior to perfusion. Oral administration of CGS 26393 attenuated SAH-induced cerebral vasospasm in a dose-dependent manner in both the prevention and reversal groups. These effects achieved statistical significance at all dosages when compared with the SAH-only or SAH plus vehicle groups. Moreover, the attenuation of vasospasm following oral administration of CGS 26393 was more efficacious than that obtained with bolus injections of CGS 26303. The levels of free CGS 26303 in the CSF were increased in a dose-dependent manner in all three CGS 26393-treated groups. This study provides the first evidence that oral administration of an inhibitor of ECE-1, CGS 26393, is capable of preventing and reversing cerebral vasospasm following SAH. These findings also reinforce evidence demonstrating that treatment with an ECE-1 inhibitor is a potentially viable therapeutic approach for reducing cerebral vasospasm after SAH.

Administration, Oral↗

PubMed2002

A quality-on-demand algorithm for wavelet-based compression of electrocardiogram signals.

For the compression of medical signals such as electrocardiogram (ECG), excellent reconstruction quality of a highly compressed signal can be obtained by using a wavelet-based approach. The most widely used objective quality criterion for the compressed ECG is called the percent of root-mean-square difference (PRD). In this paper, given a user-specified PRD, an algorithm is proposed to meet the PRD demand by searching for an appropriate bit rate in an automatic, smooth, and fast manner for the wavelet-based compression. The bit rate searching is modeled as a root-finding problem for a one-dimensional function, where an unknown rate-distortion curve represents the function and the desired rate is the root to be sought. A solution derived from root-finding methods in numerical analysis is proposed. The proposed solution is incorporated in a well-known wavelet-based coding strategy called set partitioning in hierarchical trees. ECG signals taken from the MIT/BIH database are tested, and excellent results in terms of convergence speed, quality variation, and coding performance are obtained.

Algorithms↗

PubMed2002

Wavelet-based ECG compression using dynamic vector quantization with tree codevectors in single codebook.

In this paper, we propose a novel vector quantizer (VQ) in the wavelet domain for the compression of electrocardiogram (ECG) signals. A vector called tree vector (TV) is formed first in a novel structure, where wavelet transformed (WT) coefficients in the vector are arranged in the order of a hierarchical tree. Then, the TVs extracted from various WT subbands are collected in one single codebook. This feature is an advantage over traditional WT-VQ methods, where multiple codebooks are needed and are usually designed separately because numerical ranges of coefficient values in various WT subbands are quite different. Finally, a distortion-constrained codebook replenishment mechanism is incorporated into the VQ, where codevectors can be updated dynamically, to guarantee reliable quality of reconstructed ECG waveforms. With the proposed approach both visual quality and the objective quality in terms of the percent of root-mean-square difference (PRD) are excellent even in a very low bit rate. For the entire 48 records of Lead II ECG data in the MIT/BIH database, an average PRD of 7.3% at 146 b/s is obtained. For the same test data under consideration, the proposed method outperforms many recently published ones, including the best one known as the set partitioning in hierarchical trees.

Algorithms↗

PubMedDate not supplied

Attenuation of hemolysate-induced cerebrovascular endothelial cell injury and of production of endothelin-1 and big endothelin-1 by an endothelin-converting enzyme inhibitor.

BACKGROUND: Endothelin-1 (ET-1) is a potent and long-acting vasoconstrictive peptide that has been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). ET-1 has been shown to be present in the cerebrospinal fluid of patients after SAH, and substances produced during hemolysis of subarachnoid blood clots are believed to be responsible for stimulating the production of ET-1. The biosynthesis of ET-1 is a multi-step process, involving the conversion of the relatively inactive precursor big ET-1 to the mature peptide by endothelin converting enzyme (ECE), a metalloprotease. Consequently, ECE inhibitors are expected to suppress the biosynthesis of ET-1 and reduce the pathologic impact resulting from overproduction of this peptide. The purpose of the present study was to investigate the effects of an ECE inhibitor, CGS 26303, on hemolysate-induced injury of cerebral vessel endothelial cells as well as the production of ET-1 from these cells. METHODS: Different doses of CGS 26303 and hemolysate were added to the culture medium for 48 hours. Cell injury was assessed by cell morphology and density, while the productions of ET-1 and big ET-1 were determined by radioimmunoassays. RESULTS: Hemolysate alone increased the levels of ET-1 and big ET-1 in culture medium and caused substantial cell loss. Treatment with CGS 26303 inhibited the hemolysate-induced increases in the levels of ET-1 and big ET-1 and reduced endothelial cell injury. The protective effects of CGS 26303 were modest when this inhibitor was added simultaneously with hemolysate, but were prominent and dose-dependent when the inhibitor was given 30 minutes before the addition of hemolysate. CONCLUSION: These results suggest that overproduction of ET-1 contributes significantly to hemolysate-induced damage to cerebrovascular endothelial cells.

Animals↗

PubMedDate not supplied

Acute subdural hematoma in infancy.

BACKGROUND: Acute subdural hematoma in infants is distinct from that occurring in older children or adults because of differences in mechanism, injury thresholds, and the frequency with which the question of nonaccidental injury is encountered. The purpose of this study is to analyze the clinical characteristics of acute subdural hematoma in infancy, to discover the common patterns of this trauma, and to outline the management principles within this group. METHODS: Medical records and films of 21 cases of infantile acute subdural hematoma were reviewed retrospectively. Diagnosis was made by computed tomography or magnetic resonance imaging. Medical records were reviewed for comparison of age, gender, cause of injury, clinical presentation, surgical management, and outcome. RESULTS: Twenty-one infants (9 girls and 12 boys) were identified with acute subdural hematoma, with ages ranging from 6 days to 12 months. The most common cause of injury was shaken baby syndrome. The most common clinical presentations were seizure, retinal hemorrhage, and consciousness disturbance. Eight patients with large subdural hematomas underwent craniotomy and evacuation of the blood clot. None of these patients developed chronic subdural hematoma. Thirteen patients with smaller subdural hematomas were treated conservatively. Among these patients, 11 developed chronic subdural hematomas 15 to 80 days (mean = 28 days) after the acute subdural hematomas. All patients with chronic subdural hematomas underwent burr hole and external drainage of the subdural hematoma. At follow-up, 13 (62%) had good recovery, 4 (19%) had moderate disability, 3 (14%) had severe disability, and 1 (5%) died. Based on GCS on admission, one (5%) had mild (GCS 13-15), 12 (57%) had moderate (GCS 9-12), and 8 (38%) had severe (GCS 8 or under) head injury. Good recovery was found in 100% (1/1), 75% (8/12), and 50% (4/8) of the patients with mild, moderate, and severe head injury, respectively. Sixty-three percent (5/8) of those patients undergoing operation for acute subdural hematomas and 62% (8/13) of those patients treated conservatively had good outcomes. CONCLUSIONS: Infantile acute subdural hematoma if treated conservatively or neglected, is an important cause of infantile chronic subdural hematoma. Early recognition and suitable treatment may improve the outcome of this injury. If treatment is delayed or the condition is undiagnosed, acute subdural hematoma may cause severe morbidity or even fatality.

Diagnosis, Differential↗