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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 109 records · Page 6Linked to original sources

Comparison of the Trail Making and Color Trails Tests in a Chinese context: a preliminary report.

The Color Trails Test developed as a culturally fair analogue of the Trail Making Test, was used to examine the relationship between the two tests with 35 undergraduate Chinese in Hong Kong recruited as the subjects. The scores on these two tests of the 12 men and 23 women were significantly correlated .71. The equivalence of the Trail Making and Color Trails Tests when applied to Chinese in Hong Kong was discussed.

Adult↗

Quality of life of people with epilepsy following temporal lobectomy: a preliminary report.

This is a preliminary report of the quality of life of 9 people, 5 men and 4 women, in Hong Kong who underwent temporal lobectomy for seizure control. The Chinese version of World Health Organization Quality of Life Measure Abbreviated Version, validated in Hong Kong, was used as the outcome measure. Analysis suggested that the quality of life of these participants after successful temporal lobectomy was poorer than that of 157 healthy controls in the physical and psychological domains as measured. This suggests that other factors in addition to achieving complete seizure control play significant roles in promoting the quality of life of such patients.

Adult↗

Identification of a new epitope of human IRBP that induces autoimmune uveoretinitis in mice of the H-2b haplotype.

PURPOSE: Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated disease induced by immunization with interphotoreceptor retinoid binding protein (IRBP). Major uveitogenic sites have been identified for mice of the H-2r and H-2k haplotypes but not for the H-2b haplotype. The present communication describes the characterization of an epitope contained in residues 1 to 20 of human IRBP that induces EAU in H-2b mice. METHODS: H-2b (C57BL/6, 129/J) and H-2r (BIO.RIII) mice were immunized with peptide 1-20 or with whole (bovine) IRBP. EAU (histopathology) and immunologic responses (delayed-type hypersensitivity [DTH], lymphocyte proliferation, and cytokine production) were assessed after 21 days. RESULTS: C57BL/6 mice, 129/J and (129/JxC57BL/6)F1 mice, immunized with 200 to 300 microg of peptide, developed DTH and EAU with scores comparable to those induced by 100 microg IRBP. Their lymphocytes proliferated to the peptide and produced interferon-gamma (but not interleukin-4) and transferred EAU to syngeneic recipients. Lymphocytes of IRBP-immunized mice also responded to the peptide. Peptide 1-20-immunized B1O.RIII mice failed to develop either disease or immunologic responses. CONCLUSIONS. Human IRBP peptide 1-20 contains a major epitope for the H-2b haplotype, which is apparently not presented by the H-2r haplotype.

Adoptive Transfer↗

Sequential changes in plasma cytokine and endotoxin levels in cirrhotic patients with bacterial infection.

To delineate the clinical roles of plasma cytokine or endotoxin levels in the natural course of infection in patients with decompensated cirrhosis, 66 cirrhotic patients were studied within a 1.5-year period. Plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and endotoxin were determined on days 1, 4 and 7 after admission when hospital infection was suspected and 4 months later. A total of 24 patients (36.4%) were proven to be infected during hospitalization (group A), while 42 others were not infected (group B). Fever occurred in a very high proportion (22/24) of group A patients. Baseline levels of TNF-alpha (37.7+/-15.2 compared with 8.7+/-1.2 pg/ml; P<0.01) and IL-6 (180.5+/-20.5 compared with 24.6+/-7.5 pg/ml; P<0.0001) were higher in group A patients, while IL-1beta, IL-8 and endotoxin levels were not significantly different between the two groups. For patients with hospital infection, IL-6 levels determined during the episode were significantly higher than baseline levels. Using IL-6 >80 pg/ml as a baseline cut-off level to diagnose bacterial infection, the sensitivity, specificity and accuracy were 87.5, 100 and 95.5% respectively. The one-year cumulative probability of mortality (61.1% compared with 23.7%; P<0.001) and of bacterial re-infection (72.2% compared with 18.4%; P<0.0001) was higher in group A than in group B. Plasma TNF-alpha and IL-6 levels determined at 4 months were not different between the two groups. In conclusion, fever or elevated plasma IL-6 levels in patients with decompensated cirrhosis calls for early antibiotic treatment to prevent life-threatening bacterial infection. Bacterial infection is likely to recur in those patients with increased IL-6 levels, while severe episodes of infection occur in patients with increased TNF-alpha levels.

Aged↗

Splanchnic endotoxin levels in cirrhotic rats induced by carbon tetrachloride.

BACKGROUND: Bacterial translocation (passage of intestinal bacteria to mesenteric lymph nodes) observed in cirrhosis may be a source of endotoxin that can stimulate nitric oxide production and participate in the pathogenesis of hyperdynamic circulation. Currently, there are no published data concerning splanchnic endotoxin levels in cirrhotic rats. This study was designed to determine systemic and portal hemodynamics and to detect endotoxins in the portal and systemic circulation. METHODS: Liver cirrhosis was induced by carbon tetrachloride intragastric gavage. Systemic and splanchnic endotoxin levels in control rats and cirrhotic rats with or without ascites were measured using a chromogenic Limulus assay. In addition, systemic and portal hemodynamic data were obtained using a thermodilution technique and catheterization. RESULTS: Cirrhotic rats with ascites had the lowest systemic vascular resistance (2.6 +/- 0.1 mmHg.ml-1.min.100 g body weight, BW) compared with control rats (6.3 +/- 0.3 mmHg.ml-1.min.100 g BW; p < 0.05) and cirrhotic rats without ascites (3.7 +/- 0.3 mmHg.ml-1.min.100 g BW; p < 0.05). Cirrhotic rats with ascites displayed the highest splanchnic levels of endotoxin (10.6 +/- 3.1 pg/ml) compared with cirrhotic rats without ascites (2.0 +/- 0.7 pg/ml; p < 0.05) and control rats (2.0 +/- 0.4 pg/ml; p < 0.05). There was no difference in the splanchnic endotoxin levels between control rats and cirrhotic rats without ascites (p > 0.05). Similar results were observed with systemic endotoxin values (cirrhotic rats with ascites, 10.8 +/- 2.8 pg/ml; cirrhotic rats without ascites, 2.7 +/- 0.6 pg/ml; control rats, 2.5 +/- 0.4 pg/ml; p < 0.05). A significant correlation existed between portal and systemic endotoxin values in cirrhotic rats with or without ascites (r = 0.96, p < 0.001 and r = 0.9, p < 0.05, respectively), whereas this correlation did not exist in control rats (r = 0.5, p > 0.05). CONCLUSIONS: Cirrhotic rats with ascites had the lowest systemic vascular resistance and the highest splanchnic endotoxin levels when compared with cirrhotic rats without ascites and control rats. These results suggest that splanchnic endotoxemia may be involved in the development and/or maintenance of hyperdynamic circulation.

Animals↗

Repeated episodes of spontaneous intracystic hemorrhage of hepatic cysts mimicking malignancy.

Repeated episodes of spontaneous intracystic hemorrhage in the liver are very rare. We present the case of a patient with spontaneous intracystic hemorrhage mimicking hepatic malignancy, following an episode of spontaneous hemorrhage of a cyst in the left lobe of the liver. Sonography revealed a heterogenous mass with amorphous material in one episode and a cystic mass with internal papillary projections and septations in the other. The patient experienced acute abdominal pain in the first episode and remained asymptomatic during the two-year follow-up period. With an accurate diagnosis, spontaneous hemorrhage of a hepatic cyst may follow a benign course and be treated conservatively.

Aged↗

Establishment of an animal model of hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy is a neuropsychiatric syndrome associated with acute liver failure, chronic parenchymal liver disease or portal systemic anastomosis. The spectrum of symptoms may vary from subtle mental changes to a disrupted circadian rhythm to hepatic coma. In order to investigate the possible pathogenetic mediators and the use of potential new therapies, the aim of our study was to create a reliable animal model for research on hepatic encephalopathy. METHODS: Forty male Sprague-Dawley rats were used. Fulminant hepatic failure was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg/kg) for three consecutive days (n = 30). Rats treated with normal saline served as controls (n = 10). The clinical stage of hepatic encephalopathy in TAA-treated rats was graded according to neurobehavioral testing. Spontaneous motor activities of rats were calculated using the Opto-Varimex animal activity meter. We also investigated the relationships between the neurobehavioral score and the motor activity count. RESULTS: Compared with normal, saline-treated rats, those receiving consecutive injections of TAA had apparently lower neurobehavioral scores (p < 0.001) accompanied by significantly blunted motor activities (p < 0.001). A significant correlation was demonstrated between the neurobehavioral score and total movements in rats with encephalopathy (r = 0.71, p < 0.001). In addition, the neurobehavioral score also correlated well with ambulatory movements (r = 0.73, p < 0.001) and vertical movements (r = 0.45, p < 0.05). CONCLUSIONS: The rat model is acceptable for the study of hepatic encephalopathy, as established in this study. This experimental model can be used to explore the pathogenesis and management of hepatic encephalopathy.

Animals↗

Recurrent intraocular inflammation in endotoxin-induced uveitis.

PURPOSE: Endotoxin-induced uveitis (EIU) in rats and mice peaks 24 hours after endotoxin injection and is commonly assumed to be a monophasic disease. This study examined intraocular inflammation at later time points to determine whether endotoxin injection can induce recurrent intraocular inflammation in strains of mice with high or moderate levels of susceptibility to EIU. METHODS: EIU was elicited in two mouse strains with high (C3H/HeN) and moderate (FVB/N) susceptibility, by means of intraperitoneal injections of Salmonella typhimurium endotoxin. Inflammatory cells in the anterior and posterior segments of the eye were counted by a masked observer on histologic sections of eyes from 1 to 17 days after endotoxin injection. RESULTS: A bimodal distribution of inflammatory cell infiltration was noted in eyes from C3H/HeN mice. As previously reported, inflammation peaked at 24 hours after endotoxin injection. However, a second, more pronounced peak of intraocular inflammation occurred approximately 5 days after endotoxin injection. FVB/N mice had a single peak of intraocular inflammation 4 days after injection. CONCLUSIONS: Endotoxin injection in C3H/HeN elicits recurrent intraocular inflammation. The previously unrecognized second peak of inflammation is more severe than the initial inflammatory disease. Studies on this second inflammatory peak may be useful in determining the pathogenesis of recurrent uveitis in humans.

Animals↗

A case report of Aspergillus hypersensitivity syndrome with obstructing bronchial aspergillosis.

INTRODUCTION: A 62-year-old Indian male with diabetes mellitus presented with atypical, overlap features of Aspergillus hypersensitivity syndrome and obstructing bronchial aspergillosis. CLINICAL PICTURE: He was febrile and tachypnoeic with diffuse crepitations and wheezing. Chest X-ray was normal but eosinophil count was 2900/mm3 and Ig E > 10,000 IU/ml. TREATMENT AND OUTCOME: He responded initially to high dose steroid therapy but deteriorated subsequently from extensive mucus plugging of the bronchial tree which resulted in respiratory failure and death. He was HIV-negative. CONCLUSION: Culture and histologic examination of bronchoscopically identified tracheobronchial mucus plugs should be performed as early treatment may be life-saving.

Airway Obstruction↗

Choroidal neovascularization in the rat induced by adenovirus mediated expression of vascular endothelial growth factor.

PURPOSE: To determine the effects of an adenovirus vector encoding vascular endothelial growth factor(165) (Ad.VEGF) delivered to the subretinal space in the rat. METHODS: An E1-deleted adenoviral vector encoding VEGF was injected into the subretinal space of Long-Evans rats. Immunohistochemistry identified VEGF expression. Histopathologic changes in the retina were determined by light and electron microscopy, immunohistochemistry, fluorescein angiography, and examination of wholemounts of choroid and retina. RESULTS: Increased expression of VEGF only in the retinal pigment epithelium (RPE) was detected after Ad.VEGF injection. Histopathology of these eyes revealed minimal subretinal exudation at 1 week followed by the appearance of vascular structures in the subretinal space by week 2, which persisted up to 4 weeks. Shortening of photoreceptor outer segments and reduction of the outer nuclear layer were present overlying areas of neovascularization. Fluorescein angiography of animals injected with fluorescein-dextran revealed a deep complex of new vessels. Choroidal flatmounts showed new vessel formation, verified by detection of endothelial cells via immunohistochemistry, arising from the choroid with absence of change in the overlying retinal vasculature. Electron microscopy confirmed the presence of sub-RPE endothelial cells and pericytes and the loss of integrity of Bruch's membrane, and serial sectioning demonstrated choroidal vascular growth through Bruch's membrane. CONCLUSIONS: These results support the hypothesis that overexpression of VEGF from RPE cells is capable of inducing choroidal neovascularization in the rat and provide a framework for further examining angiogenic processes in the RPE-choroid complex.

Adenoviruses, Human↗

Selective potentiating effect of RS14203 on a serotoninergic pathway in anesthetized rats.

The usefulness of selective inhibitors of type 4 phosphodiesterase (PDE4) in the treatment of inflammation and pulmonary diseases is limited by their side effects: nausea and vomiting. We studied the effect of three structurally diverse PDE4 inhibitors on the vagal nerve afferent and efferent fibers in anesthetized rats. The effects of RS14203, (R)-rolipram, and CT-2450 were evaluated on the von Bezold-Jarisch reflex (vagal afferent fibers) and in a model of vagal electrical stimulation (vagal efferent fibers). All three PDE4 inhibitors were administered at 1, 10, or 100 microg/kg (iv) 15 min prior to the induction of bradycardia by an iv injection of 2-methyl-5-HT (von Bezold-Jarisch reflex) or by vagal electrical stimulation. At 100 microg/kg, RS14203 significantly potentiated the 2-methyl-5-HT response. No statistically significant effects were observed with (R)-rolipram or CT-2450 at the doses studied. RS14203, (R)-rolipram, or CT-2450 (1-100 microg/kg iv) did not affect the bradycardia induced by vagal electrical stimulation. Consequently, our results show that RS14203 selectively facilitates serotoninergic neurotransmission in vagal afferent fibers. The emetic action of RS14203 may be mediated by this mechanism.

Afferent Pathways↗

Splanchnic hyposensitivity to glypressin in a haemorrhage/transfused rat model of portal hypertension: role of nitric oxide and bradykinin.

Hyposensitivity to vasopressin is a well documented phenomenon in animals with portal hypertension and patients with cirrhosis subject to haemorrhage. Haemorrhage is associated with the endogenous release of bradykinin, which may subsequently stimulate the formation of nitric oxide (NO). The present study investigated the relative contribution of NO synthase (NOS) isoforms and the role of bradykinin in the pathogenesis of splanchnic hyposensitivity to a long-acting vasopressin analogue, glypressin, in rats with portal hypertension induced by partial portal vein ligation (PVL). At 14 days after the operation, systemic and portal haemodynamics were measured in stable or bleeding PVL rats receiving an intravenous infusion of glypressin (0.07 mg/kg). In the treatment groups, N(G)-nitro-L-arginine methyl ester (L-NAME; a non-selective NOS inhibitor), L-canavanine (a specific inhibitor of inducible NOS) or HOE 140 (a bradykinin B(2) receptor antagonist) was administered 45 min before the infusion of glypressin. In rats with a hypotensive haemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was re-infused before the administration of glypressin or various inhibitors. Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage/transfused PVL rats. The infusion of L-NAME elevated the mean arterial pressure in the bleeding PVL rats without the modulation of portal pressure. The addition of L-NAME or HOE 140, but not L-canavanine, significantly and similarly potentiated the portal-hypotensive effects of glypressin. It is concluded that constitutive NOS and bradykinin are responsible, at least partly, for the splanchnic hyposensitivity to glypressin observed in the early stages of the haemorrhage/transfused rat model of portal hypertension.

Animals↗

Apoptosis in cytomegalovirus retinitis associated with AIDS.

PURPOSE: To determine the role of apoptosis in the pathogenesis of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. METHODS: Forty-three eyes from patients with cytomegalovirus retinitis treated before the introduction of highly active anti-retroviral therapy were examined by routine histopathology and in situ techniques to detect apoptosis (TUNEL assay). Apoptosis was graded on a scale from 0 to 3+ by quantitating the number of TUNEL positive cells per case using a standard grading procedure. Statistical analysis describing the association between apoptosis grade and the proportions of eyes with active CMV infection, with choroidal inflammation and treated with the sustained-release intravitreal ganciclovir implant was performed using the Armitage procedure. RESULTS: Apoptosis in both CMV infected and uninfected retinal cells was detected in 28 of 41 eyes (68%); 13 (45%) with active and 15 (55%) with inactive cytomegalovirus retinitis. The degree of apoptosis was mild (1+) in 14 eyes, moderate (2+) in 6 eyes and severe (3+) in 8 eyes. Apoptosis was not identified in two eyes without CMVR. An increase in apoptosis grade was positively associated with active CMVR (p = 0.014). There was no significant association between apoptosis and choroidal inflammation. The presence and the severity of apoptosis was less in eyes treated with the sustained-release intravitreal ganciclovir implant compared to those treated with systemic anti-viral therapy, however, the difference was not statistically significant. CONCLUSIONS: Apoptosis contributes to retinal cell loss in eyes with cytomegalovirus retinitis associated with AIDS but did not correlate with the progressive loss of retinal cell function in patients with treated, inactive CMVR.

AIDS-Related Opportunistic Infections↗

Analysis of cytokine dynamics in corneal allograft rejection.

Motivated by the discovery of oscillations in tumour necrosis factor-alpha (TNF-alpha) concentration in the aqueous humour of rabbits undergoing corneal allograft rejection, a simple mathematical model is developed for the regulation of TNF-alpha, which incorporates both negative feedback and amplification pathways. Mathematical analysis reveals a surprisingly rich behavioural repertoire for this simple cytokine pathway, including excitability, threshold behaviour, hysteresis, oscillations and bistability. This suggests new possibilities for experimental demonstration, and reveals the potential contributions of nonlinear dynamics to understanding cytokine regulation.

Animals↗

Substituted indoles as potent and orally active 5-lipoxygenase activating protein (FLAP) inhibitors.

This paper reports on the SAR investigation of inhibitors of 5-lipoxygenase activating protein (FLAP) based on MK-0591. Emphasis was made on modifications to the nature of the link between the indole and the quinoline moieties, to the substitution pattern around the two heterocycles and to possible replacements of the quinoline moiety. Lead optimization culminated in (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(pyridin-2-ylmethoxy)-ind ol-2-yl]-2,2-dimethylpropanoic acid (18k), as a potent inhibitor of leukotriene biosynthesis that is well absorbed and active in functional models.

5-Lipoxygenase-Activating Proteins↗