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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 55 records · Page 3Linked to original sources

Detection of Toxoplasma gondii DNA in primary intraocular B-cell lymphoma.

Primary intraocular lymphoma, a variant of primary central nervous system lymphoma with ocular involvement, is a large B-cell non-Hodgkin's lymphoma. Some cases of primary intraocular lymphoma have been reported to be associated with microorganisms including Epstein-Barr virus (EBV) and human herpes virus-8 (HHV-8), but not parasites. We analyzed 10 cases of primary intraocular lymphoma using microdissection and PCR. Tumor and normal cells were microdissected from ocular tissue on slides and subjected to PCR for genes from Toxoplasma gondii, EBV, and HHV-8. We detected Toxoplasma gondii, not HHV-8 or EBV, DNA in the lymphoma but not in normal cells of two cases that resembled ocular toxoplasmosis clinically. We speculate that Toxoplasma gondii may play a role in some forms of primary intraocular B-cell lymphoma.

Adult↗

Inhibition of prostacyclin by indomethacin ameliorates the splanchnic hyposensitivity to glypressin in haemorrhage-transfused common bile duct-ligated rats.

Prostacyclin (PGI2) is an important contributor to the mediation of hyporeactivity to vasoconstrictors and the development of hyperdynamic circulation in portal hypertensive states. Inhibition of PGI2 synthesis in haemorrhage-transfused partially portal vein-ligated rats could ameliorate the splanchnic hyposensitivity to glypressin, a long-acting vasopressin analogue. This study investigated whether the hyposensitivity to glypressin also exists in rats with common bile duct ligation (BDL) and whether the inhibition of PGI2 synthesis by indomethacin could potentiate the portal-hypotensive effect of glypressin in bleeding BDL rats. Two series of BDL rats were used. Series 1 investigated the haemodynamic effects of low dose glypressin (0.07 mg kg-1) in BDL rats with or without bleeding by catheterization. In series 2, haemodynamic parameters were measured in stable or bleeding BDL rats that were receiving intravenously high dose glypressin (0.2 mg kg-1) or indomethacin (5 mg kg-1) followed by high dose glypressin. In rats with a hypotensive haemorrhage, 4.5 mL of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or indomethacin. Splanchnic hyposensitivity to glypressin was demonstrated in haemorrhage-transfused BDL rats receiving high, but not low, doses of glypressin. Indomethacin infusion did not cause significant systemic and portal haemodynamic changes in bleeding BDL rats (P > 0.05). The addition of indomethacin significantly enhanced the portal-hypotensive effects of glypressin (P < 0.05) and potentiated the increases in mean arterial pressure induced by glypressin infusion (P < 0.001) in bleeding BDL rats. Splanchnic hyposensitivity to glypressin observed in haemorrhage-transfused BDL rats could be ameliorated by the addition of indomethacin, suggesting a role of endogenous PGI2 in its pathophysiology.

Animals↗

Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure.

Hepatic encephalopathy is a complex neuropsychiatric syndrome seen secondary to acute liver failure, chronic parenchymal liver disease, or portal-systemic anastomosis. Vasodilatation induced by nitric oxide (NO) may be involved in the development of hepatic coma. However, there are no comprehensive data concerning the effects of NO inhibition on the severity of hepatic encephalopathy. Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg kg-1 day-1) for 3 days. Rats were divided into two groups to receive either NG-nitro-L-arginine methyl ester (L-NAME, 20 mg kg-1 day-1 via intragastric gavage) or normal saline (N/S) from 2 days prior to TAA administration for 5 days. Severity of encephalopathy was assessed by counts of motor activity and neurobehaviour test scores. Plasma levels of endotoxin, tumour necrosis factor-alpha and nitrate/nitrite were determined by the chromogenic Limulus assay, enzyme-linked immunosorbent assay and colorimetric assay, respectively. Compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving L-NAME (59% vs. 18%, P < 0.01). Inhibition of NO had detrimental effects on the counts of motor activities (P < 0.05) and neurobehaviour score (P < 0.01). Rats treated with L-NAME had significantly higher plasma levels of endotoxin (26.7 +/- 3.8 pg mL-1) and tumour necrosis factor-alpha (29.4 +/- 6.5 pg mL-1) compared with rats treated with N/S (13.2 +/- 2.7 pg mL-1 and 11.2 +/- 2.6 pg mL-1, respectively, P < 0.01). Plasma levels of endotoxin and tumour necrosis factor-alpha, but not of nitrate/nitrite, were significantly correlated with the severity of hepatic encephalopathy (P < 0.05). Chronic L-NAME administration had detrimental effects on the severity of encephalopathy in TAA-treated rats, suggesting a protective role of NO in the development of fulminant hepatic failure.

Animals↗

Carotid dissection: a common cause of Horner's syndrome.

PURPOSE: To highlight that internal carotid artery dissection is a common cause of Horner's syndrome and that it is important to diagnose dissection as anticoagulation can prevent carotid thrombosis and embolism. METHODS: Five case reports are presented of patients with Horner's syndrome secondary to carotid dissection. One patient had carotid dissection secondary to trauma, two had spontaneous dissections and two had dissections in the settings of other illness. A literature search was performed on carotid dissection as a cause of Horner's syndrome and its diagnosis and management. RESULTS: The case reports and literature highlight that dissection is under-recognized as a cause of Horner's syndrome and can be missed. The investigation of choice is a magnetic resonance imaging and angiography scan of the head and neck. The treatment advocated is anticoagulation for 3-6 months. CONCLUSION: Carotid dissection should be suspected in patients with Horner's syndrome, particularly if head or neck pain is present.

Anticoagulants↗

Endothelin-1 induces vasoconstriction on portal-systemic collaterals of portal hypertensive rats.

Portal hypertension is associated with increased hepatic and collateral resistance to an increased portal blood flow. Endothelin-1 (ET-1) can induce intrahepatic vasoconstriction and consequently increase portal pressure. It is unknown if ET-1 also modulates portal pressure by a direct vasoconstrictive effect on collaterals. This study investigated the collateral vascular responses to ET-1, the receptors in mediation, and the regulation of ET-1 action by nitric oxide and prostaglandin. The portal-systemic collaterals of partially portal vein-ligated rats were tested by in situ perfusion. The concentration-response curves of collaterals to graded concentrations of ET-1 (10(-10)-10(-7) mol/L) with or without BQ-123 (ET(A) receptor antagonist, 2 x 10(-6) mol/L), BQ-788 (ET(B) receptor antagonist, 10(-7) mol/L) or both were recorded. In addition, the collateral responses to ET-1 with preincubation of n(omega)-nitro-L-arginine (NNA; 100 mol/L), indomethacin (INDO; 10 mol/L), or in combination were performed. ET-1 increased the perfusion pressure of collaterals and its effect was significantly suppressed by BQ-123 alone and BQ-123 plus BQ-788, but not BQ-788 alone (P <.05). Incubation with NNA, INDO, or both significantly enhanced the response of collaterals to ET-1 (P < .05). These results show that ET-1 produces a direct vasoconstrictive effect on the collateral vessels of portal hypertensive rats. This effect is mediated by ET(A,) but not ET(B), receptors. Both nitric oxide and prostaglandin modulate the collateral vascular response to ET-1 and may therefore participate in the development and maintenance of portal hypertension.

Animals↗

Ethnic differences in anthropometry among adult Singaporean Chinese, Malays and Indians, and their effects on lung volumes.

When standing height (StndHt) cannot be assessed, arm span (AS) or sitting height (SitHt) has been used as surrogate variables for prediction of StndHt in adult caucasians and blacks. We examined (1) the relationship between StndHt, AS and SitHt among adult Chinese, Malays and Indians; and (2) whether anthropometry could explain the ethnic differences in lung volumes (as StndHt-adjusted lung volumes are known to differ significantly: Chinese > Malays > Indians). We recruited 1250 consecutive outpatients aged 20-90 years. Prediction equations of StndHt (with AS, SitHt, weight, age as predictors) for each subgroup of race and sex were formulated with multiple linear regressions. Equations with both AS and SitHt as predictors had the best goodness of fit (SEE = 2.37-2.85 cm, adjusted R2 = 0.67-0.87), as compared to equations with either AS (SEE = 3.00-3.91 cm, adjusted R2 = 0.58-0.80) or SitHt alone (SEE = 3.48-4.00 cm, adjusted R2 = 0.45-0.76). GLM general factorial analyses found that age- and weight-adjusted SitHt-to-StndHt ratios differed significantly among Chinese (0.539), Malays (0.529) and Indians (0.518). This paralleled the ethnic differences in lung volumes. The equations with both AS and SitHt as predictors provide the most accurate estimate of StndHt. Ethnic differences in upper body segment length may explain in part the lung volume differences.

Adult↗

Relationship of motor and cognitive abilities to functional performance in stroke rehabilitation.

This study explored the relationships between the motor and cognitive abilities, and the functional performance of patients with stroke. Motor and cognitive abilities were measured by the Fugl-Meyer Assessment (FMA) and the Neurobehavioural Cognitive Status Examination (NCSE), and functional performance was measured by the Functional Independence Measure (FIM). All assessments were conducted at admission, after 2 and 4 weeks, and at discharge. A total of 37 patients with first stroke at mean age 62.3 years (SD=5.4) participated in the study. Results indicated that the lower extremity and balance scores on the FMA were highly correlated with the FIM (motor subscale) on all occasions (r = 0.65--0.92), whereas upper extremity and hand scores on the FMA were moderately correlated (r = 0.53--0.73). Cognitive abilities such as judgement, comprehension and repetition had moderate positive relationships with functional performance (r = 0.35--0.62). Consistent with previous studies, motor functional performance at discharge was best predicted by balance and judgement abilities at admission, or lower extremity abilities and balance at 2-weeks, or lower extremity and repetition abilities at 4-weeks. At admission, lower extremity and cognitive abilities were found to be the best predictors of patients' length of stay. The results from this study substantiated the fact that motor impairment, including balance and lower limb ability, strongly accounts for functional recovery in the rehabilitation of patients with stroke staying in hospital. This study provided good data for rehabilitation professionals on monitoring neurological recovery, especially balance and lower extremity abilities, to enhance the functional recovery of patients after stroke. More intensive intervention in these aspects should be provided to patients to promote more efficient functional regain and shortening of the length of stay.

Activities of Daily Living↗

Biodosimetry using chromosomal translocations measured by FISH in a population chronically exposed to low dose-rate 60Co gamma-irradiation.

PURPOSE: To evaluate the cumulative gamma-radiation personal exposure by analysing lymphocyte chromosome translocations using FISH painting and to compare FISH-derived biodoses with those derived from retrospective physical dose reconstruction in residents receiving chronic low dose-rate gamma-irradiation while living in radio-contaminated buildings. MATERIALS AND METHODS: Chromosome translocation frequencies were evaluated by scoring 933 to 3077 metaphases under fluorescence microscope for each of the five male and four female exposed individuals after they had relocated from the radioactive environment for 34-82 months. FISH painting was conducted using kits of whole-chromosome probes for chromosomes 1, 2 and 4 in orange and 3, 5 and 6 in green and counter-stained with 4',6-diamidino-2-phenylindole (DAPI). The retrospective dose estimation termed Taiwan Cumulative Dose (TCD) was conducted by assessment using detailed information of historical exposure and the environmental radioactivity for each apartment during previous residency. RESULTS: A total of 20 244 well-prepared metaphases were scored. Biodoses were calculated from the translocation frequencies and physical doses were estimated from detail questionnaires for each individual. The translocation frequencies measured ranged from 2.2x10(-3) to 26.8x10(-3) translocations per cell and the dose equivalent from 52.2 to 992.2mSv. A good correlation was observed between the physical and biodoses. A plot of TCD against FISH-derived doses produced D(fish) =0.65 D(TCD), when fitted by a linear model, and D(fish) = 0.53 D(TCD)+ 1.26x10(-4 ) D(2)(TCD), when fitted with a linear-quadratic model. Given the scatter in the data and the extremely small quadratic dose contribution, neither model could be ruled out. CONCLUSION: Chromosome translocations provide a valid method of dose estimation in extremely protracted low dose-rate gamma-radiation exposure. Validation of the TCD method by FISH-measured translocations supports the use of TCD for epidemiological studies.

Adolescent↗

An approach to modelling in immunology.

Like most other fields in biology, immunology has been revolutionised by the techniques of molecular biology and the resulting explosion in available experimental data. It is argued that efforts to integrate the data to gain insight into how various subsystems in the immune system interact and function require mathematical modelling and computer simulation in close collaboration with experimentalists. This paper illustrates some of the techniques available for modelling immune systems, and highlights the issues that should be borne in mind by anyone starting down the modelling path.

Animals↗

Smoking status and body size increase carbon monoxide concentrations in the breathing circuit during low-flow anesthesia.

The major sources for intraoperative carbon monoxide (CO) in the breathing circuit are related to patient's hemoglobin catabolism, smoking and the degradation between absorbent and anesthetics. We performed this study to evaluate their combined effects on CO production during low-flow anesthesia. We used a direct-measurement instrument to measure real-time CO concentrations in the breathing circuit during different anesthetic conditions for patients who received desflurane or isoflurane. By applying multiple linear regression models, we determined the significant factors related to CO concentrations in the circuit. We identified patients' smoking status, preoperative smoking and body weight as well as gas flow rates as important factors for affecting peak and time-weighted CO levels. These four factors predicted approximately 44.1% and 42.7% of peak and mean inspiratory CO concentrations respectively. We found that chronic and preoperative smokers and patients with larger body weights are associated with increased CO concentrations, whereas increase in gas flow rates could decrease CO concentrations. After controlling these four important factors, we found that inspiratory CO concentrations were not significantly associated with the choice of anesthetic and its concentration during low-flow anesthesia.

Adolescent↗

Ocular manifestations of central nervous system lymphoma.

Primary intraocular lymphoma (PIOL) is a variant of primary central nervous system lymphoma in which lymphoma cells are initially present only in the eyes without evidence of disease in the brain or cerebrospinal fluid. Patients with PIOL are typically older adults who present with blurred vision and floaters. The ophthalmic examination characteristically shows a cellular infiltrate in the vitreous with or without the presence of subretinal infiltrates. Diagnostic evaluation for PIOL includes neuroimaging, cytologic examination of the cerebrospinal fluid, and a diagnostic vitrectomy with special handling of the vitreous specimen, if the former is nondiagnostic. Molecular and cytokine analyses are useful adjuncts to cytology for the diagnosis of PIOL. Recent molecular studies demonstrating viral DNA in the ocular lymphoma cells suggest a role for infectious agents in the pathogenesis of PIOL. To date, the best mode for treatment of PIOL or recurrent primary central nervous system lymphoma involving only the eyes remains undefined.

Adolescent↗

Consistency of performance on the functional capacity assessment: static strength and dynamic endurance.

OBJECTIVE: To explore the degree of consistency in a subject's performance in physical strength and endurance. DESIGN: Thirty healthy men, aged 19 to 26 yr, were recruited to participate in protocols to assess static strength and dynamic endurance tests on their upper limbs with the Baltimore Therapeutic Equipment Primus. Retests were conducted 7 days after the initial test. RESULTS: The intraclass correlation coefficients were 0.71 to 0.97 and 0.32 to 0.90 for static and dynamic endurance strengths, respectively. These results indicated that the consistency of the subjects' performance across occasions was high for testing static strength, although it was more varied for testing endurance strength. CONCLUSIONS: Higher consistency was observed among subjects in the assessment of static strength than dynamic endurance strength. The range of motion traveled by the limb, speed of performance, and ergonomic design of attachments seemed to confound the subjects' performance on the instrument. Stringent assessment protocols, ergonomically designed hardware, and clear instructions and practice trials before the formal testing were essential to maximize the subjects' consistency of performance. The results of this study were applicable and generalized to other performance-based instruments for physical and functional capacity evaluation and work simulators.

Activities of Daily Living↗

Steroid management in giant cell arteritis.

AIM: Ocular involvement in giant cell arteritis (GCA) is an ophthalmic emergency which, if untreated, can progress to permanent blindness. There is little evidence in the literature to support current protocols for the acute treatment of GCA with steroids. The authors sought to review the effects of intravenous and oral steroids in GCA. METHODS: This retrospective study reviewed the records of 100 consecutive patients with biopsy proved giant cell arteritis. 73 patients with visual loss who were treated at the Royal Victorian Eye and Ear Hospital (RVEEH) and St Vincent's Hospital were included in the final series. The authors studied the management of the patients in the first week after presentation, analysing types of treatment, dose, effect on visual acuity, and complications. RESULTS: All the patients except one had visual loss due to anterior ischaemic optic neuropathy (AION). 17 patients (23%) had bilateral eye involvement. Visual acuity improved in 21 of 73 patients (29%) by a mean of two Snellen chart lines after commencement of steroids. There was an increased likelihood of improved vision in the group who had intravenous steroids (40%) compared with those who received oral steroids (13%). In all except four patients (95%) vision remained stable at 1 month review. CONCLUSIONS: Prompt treatment of GCA with steroids leads to improvement of visual acuity in a significant number of cases. Intravenous steroids may offer a greater prospect of improvement compared with oral steroids. A prospective trial comparing intravenous with oral steroids is needed to validate these findings and would not expose elderly patients to unacceptable risks.

Administration, Oral↗

Helicobacter pylori infection induced alteration of gene expression in human gastric cells.

BACKGROUND: Helicobacter pylori, a human pathogen responsible for many digestive disorders, induces complex changes in patterns of gene expression in infected tissues. cDNA expression arrays provide a useful tool for studying these complex phenomena. AIM: To identify genes that showed altered expression after H pylori infection of human gastric cells compared with uninfected controls. METHODS: The gastric adenocarcinoma cell line AGS was cocultivated with H pylori. Growth of infected cells was determined by trypan blue exclusion assay. Complementary DNA probes derived from H pylori treated and untreated cells were hybridised to two identical Atlas human cDNA expression arrays, and those genes with altered expression levels were identified. A real time quantitative reverse transcription-polymerase chain reaction assay was used to better define expression patterns of these genes in endoscopically gastric mucosal biopsies with and without H pylori infection. RESULTS: Over 24 hours, coincubation with H pylori inhibited AGS cell growth but did not cause a noticeable degree of cell death. H pylori treatment altered the pattern of gene expression in AGS cells. We identified 21 overexpressed genes and 17 suppressed genes from the cDNA expression arrays. The majority of genes were transcription factors such as c-jun, BTEB2, and ETR101. Other genes were involved in signal transduction pathways, such as MAP kinase, interleukin 5, and insulin-like growth factor. Genes involved in cell cycle regulation and differentiation, such as CDC25B and NM23-H2, were also identified. In patients with H pylori infection (n=20), there was a significant difference for ERCC3, Id-2, and NM23-H2 mRNA levels in infected gastric mucosa compared with uninfected gastric mucosa in patients without peptic diseases (n=20) (ERCC3 4.75 molecules/10(4) beta-actin mRNA molecules v 13.65, p<0.001; Id-2 16.1 v 23.4, p<0.05; NM23-H2 17.5 v 45.5, p<0.001). There was no significant difference between mRNA levels of c-jun and CDC25B in H pylori colonised gastric mucosa and uninfected mucosa. CONCLUSION: We demonstrated that H pylori infection caused alteration of gene expression in AGS cells. The differential hybridisation technique of Atlas human cDNA expression array is a useful method to identify host genes involved in pathogenic mechanisms in H pylori infection.

Apoptosis↗

Evidence for stretch-induced resistance increase of proximal coronary microcirculation.

We investigated the influence of stretch on regional hemodynamic parameters of the septal circulation. We used a similar experimental setup and mathematical model, as described previously (14). Five ventricular septa were isolated from anesthetized dogs, sutured to a biaxial stretching apparatus, and perfused with an oxygenated perfluorochemical emulsion at maximal vasodilation. Under unloaded and biaxially stretched conditions, flow and septal thickness (to index vascular volume) were measured continuously. Pressure was varied sinusoidally at 30, 50, and 70 mmHg with amplitude of 7.5 mmHg over frequencies ranging between 0.015 and 7 Hz. Admittance (flow/pressure) and capacitance (thickness/pressure) transfer functions were calculated and interpreted in terms of a two-compartmental model with volume-dependent resistances. Parameter estimation showed that the proximal resistance and compliance were unaffected, whereas the resistance of the proximal part of the microcirculation, including the small arterioles, increased with stretch. The effect of stretch on the distal resistance and capacitance, however, could not be determined unequivocally.

Animals↗

Molecular analysis of primary central nervous system and primary intraocular lymphomas.

Primary central nervous system lymphoma (PCNSL) is usually a large B-cell, high grade non-Hodgkin's lymphoma (NHL) classified as a diffuse large cell lymphoma (DLCL). In rare cases, however, T cell lymphomas have been described. Although a relatively rare tumor, the incidence of PCNSL has increased dramatically over the past 15 years in both immuno-competent and immunocompromised patients. The disease is aggressive with a 5-year survival rate of less than 25 %. The cause of death is progressive and recurrent disease in the CNS, despite aggressive treatment. Approximately 20-25% of patients with PCNSL also have primary intra-ocular lymphoma (PIOL). PCNSL and PIOL are closely related and inter-connected pathologies involving two immune privileged sites. The study of PCNSL and PIOL has been limited due to the fact that viable malignant cells are rare and difficult to recognize. Moreover, the cells are difficult to culture and to date there is no good animal model for the disease. Here, we will present the current literature on the disease. In particular, we will present data suggesting that PCNSL in immuno-compromised and AIDS patients may correspond to two different pathologies. Furthermore, we will discuss how the study of these lymphomas can benefit from new advanced molecular biology techniques including single cell PCR and laser capture microdissection (LCM). PCNSL and PIOL are aggressive tumors, therefore, early diagnosis and prompt, aggressive treatment may improve prognosis. Advanced molecular biology will help delineate the oncogenesis of PCNSL and PIOL.

Animals↗

In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats.

OBJECTIVE: To determine potency and selectivity of nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase- (COX-) specific inhibitors in whole blood from horses, dogs, and cats. SAMPLE POPULATION: Blood samples from 30 healthy horses, 48 healthy dogs, and 9 healthy cats. PROCEDURE: Activities of COX-1 and COX-2 were determined by measuring coagulation-induced thromboxane and lipopolysaccharide-induced prostaglandin E2 concentrations, respectively, in whole blood with and without the addition of various concentrations of phenylbutazone, flunixin meglumine, ketoprofen, diclofenac, indomethacin, meloxicam, carprofen, 5-bromo-2[4-fluorophenyl]-3-14-methylsulfonylphenyl]-thiophene (DuP 697), 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furan one (DFU), 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone (MF-tricyclic), and celecoxib. Potency of each test compound was determined by calculating the concentration that resulted in inhibition of 50% of COX activity (IC50). Selectivity was determined by calculating the ratio of IC50 for COX-1 to IC50 for COX-2 (COX-1/COX-2 ratio). RESULTS: The novel compound DFU was the most selective COX-2 inhibitor in equine, canine, and feline blood; COX-1/COX-2 ratios were 775, 74, and 69, respectively. Carprofen was the weakest inhibitor of COX-2, compared with the other COX-2 selective inhibitors, and did not inhibit COX-2 activity in equine blood. In contrast, NSAID such as phenylbutazone and flunixin meglumine were more potent inhibitors of COX-1 than COX-2 in canine and equine blood. CONCLUSIONS AND CLINICAL RELEVANCE: The novel COX-2 inhibitor DFU was more potent and selective in canine, equine, and feline blood, compared with phenylbutazone, flunixin meglumine, and carprofen. Compounds that specifically inhibit COX-2 may result in a lower incidence of adverse effects, compared with NSAID, when administered at therapeutic dosages to horses, dogs, and cats.

Animals↗