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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 163 records · Page 9Linked to original sources
PubMed1999

Use of microdissection and molecular genetics in the pathologic diagnosis of retinoblastoma.

BACKGROUND/PURPOSE: Retinoblastoma results from mutations or loss of both alleles of the retinoblastoma gene. Although retinoblastoma is usually recognized clinically, some forms of the disease can elude diagnosis. The purpose of this study was to determine whether the use of molecular genetics to detect a loss of heterozygosity (LOH) in the retinoblastoma gene could assist the ocular pathologist in the diagnosis of this malignancy. METHODS: Deoxyribonucleic acid (DNA) was obtained from tumor cells microdissected from three ocular specimens from two patients with diffuse retinoblastoma. Polymerase chain reaction was used to detect two microsatellite markers (D13S153 and D13S118) of the retinoblastoma gene. Loss of heterozygosity was identified when one of the two polymorphic alleles was present in the DNA from normal tissue but absent or reduced in the DNA obtained from tumor cells. RESULTS: Loss of heterozygosity was identified in all three specimens from the two patients with diffuse retinoblastoma. In one patient, the diagnosis of retinoblastoma was based on identification of LOH from tumor cells obtained from vitrectomy. CONCLUSIONS: This study demonstrates that identification of LOH in retinoblastoma cells not only can contribute to our understanding of the molecular genetics of this tumor, but also can help the ocular pathologist in the diagnosis of atypical forms of the disease.

Adolescent↗
PubMed1999

Is the vacuum extractor really the instrument of first choice?

This study was a retrospective analysis of the pattern of usage of both the forceps and vacuum extractor as well as the neonatal outcome on all the instrumental deliveries conducted in 1995 at the Kandang Kerbau Hospital, Singapore. There were a total of 927 forceps deliveries and 495 vacuum extractions but neonatal data was available for only 481 forceps and 255 vacuum extractor babies. (There were 2 neonatal units which accepted admissions on alternate days; all of the data were collected from 1 of the units only). Demographic data were comparable in most aspects except that vacuum deliveries were significantly associated with higher parity and shorter labours. There was a trend towards using the vacuum extractor in less difficult cases. Almost all the instrumental deliveries were conducted by specialists. Birth trauma was significantly more likely to occur with the vacuum extractor. Almost all the deliveries were conducted with similar expertise in both groups, yet the use of the vacuum extractor resulted in more birth trauma even in the presence of 'easier' cases. This may suggest an inherent risk in using the vacuum extractor.

Adult↗
PubMed1999

Role of substance P in the pathogenesis of spider angiomas in patients with nonalcoholic liver cirrhosis.

OBJECTIVE: Cutaneous spider angioma is a common sign observed in patients with liver cirrhosis, but its pathogenesis is still unclear. Increased plasma levels of estrogen, vascular dilation, and neovascularization are possible etiologies. This study was designed to investigate the relationship of spider angiomas in patients with nonalcoholic liver cirrhosis to the plasma levels of sex hormones and various vasodilators and hemodynamic parameters. METHODS: A total of 60 patients with nonalcoholic liver cirrhosis and 20 healthy subjects were included in this study. The number, size, and location of the spider angiomas were recorded. Plasma levels of estradiol, testosterone, substance P, calcitonin gene-related peptide, and nitrate/nitrite and forearm hemodynamics were measured. RESULTS: Cirrhotic patients showed higher plasma estradiol/testosterone ratios (28.3+/-47.2 x 10(-3), median 10.5 x 10(-3) vs 8.2+/-8.3 x 10(-3), median 5.7 x 10(-3), p = 0.003) and levels of nitrate/ nitrite (29.9+/-17.5, median 23.8 vs 21.4+/-10.0, median 20.6 micromol/L, p = 0.01) and substance P (47.5+/-62.5, median 29.2 vs 15.2+/-7.7, median 12.3 pg/ml, p < 0.001) than healthy controls. Sixteen (27%) of the 60 cirrhotic patients had spider angiomas. Cirrhotic patients with spider angiomas disclosed higher plasma levels of substance P (84.7+/-105.3, median 53.1 vs 34.5+/-30.7, median 25.8 pg/ml, p = 0.006) and serum levels of bilirubin (3.9+/-3.8, median 1.9 vs 1.9+/-1.9, median 1.2 mg/dl, p = 0.02) than those without. Stepwise logistic regression showed substance P was the only significant and independent predictor associated with the presence of spider angiomas in cirrhotic patients (odds ratio = 3.0, 95% confidence interval = 1.4-6.6, p = 0.01). CONCLUSION: Plasma levels of substance P are elevated in patients with nonalcoholic cirrhosis and may play an important role in the pathogenesis of spider angiomas.

Aged↗
PubMed1999

Dose-response relationship of phototherapy for seasonal affective disorder: a meta-analysis.

OBJECTIVE: The therapeutic effect of phototherapy for seasonal affective disorder (SAD) has been widely investigated. However, the antidepressant effect of various light intensities is inconclusive. The purpose of this study was to evaluate the dose-response relationship of phototherapy for SAD. METHOD: A meta-analytical methodology was applied to 39 studies of phototherapy for SAD. The studies collected were screened for study quality by a threats-to-validity method before inclusion. The fixed-effects-model analysis of variance procedures were used for data analysis. RESULTS: The results indicated that different light intensities produced different effects in reducing the typical symptoms, as measured by the Hamilton Depression Rating Scale, of patients with SAD. However, no significant differences in these effects were revealed between strong, medium and dim light in reducing the atypical symptoms of patients. CONCLUSION: These findings showed that light intensity varied positively with the antidepressant effect for typical but not for atypical symptoms of SAD, suggesting that light intensity tended to have different therapeutic effects on the typical and atypical symptoms of SAD.

Dose-Response Relationship, Drug↗
PubMed1999

Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma.

AIM: To develop and assess a protocol for the treatment of intraocular lymphoma by intravitreal injection of methotrexate and thiotepa. METHODS: A patient with intraocular non-Hodgkin's lymphoma which recurred after radiotherapy and repeated systemic chemotherapeutic regimens underwent repeated intravitreal injections of methotrexate and thiotepa. The patient was closely monitored by cytology, anterior chamber flare measurements, IL-10 and IL-6 levels. Methotrexate drug clearance studies were performed on vitreous samples taken before each injection. RESULTS: Complete tumour clearance was achieved by the third week of therapy. IL-10 and IL-6 levels quickly dropped to barely detectable levels as the tumour was cleared from the eye. Flare measurements decreased from 500 to 15 photons/s over the same time. A plot of the methotrexate levels over time revealed a first order kinetic rate of elimination with an effective tumoricidal intravitreal dose persisting for 5 days after injection. CONCLUSION: Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma appears effective in prolonging local remission of ocular disease even in the presence of an aggressively growing tumour. A single intravitreal injection of methotrexate can lead to a prolonged tumoricidal concentration lasting for a longer period than that achieved by systemic administration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Short-term effect of ozone on the pulmonary function of children in primary school.

The objective of this study was to evaluate the short-term effect of ambient air pollution on the pulmonary function of schoolchildren. We sampled 941 children in primary school in three communities in Taiwan (Sanchun, Taihsi, and Linyuan). The nearby stations of the Taiwan air quality monitoring network provided the hourly ambient concentrations of sulfur dioxide, carbon monoxide, ozone, particulate matter < or = to 10 microm in aerodynamic diameter, and nitrogen dioxide. Spirometry was performed once for each sampled child. We also obtained the status of indoor air pollution and chronic respiratory disease history by using a structured questionnaire. Multivariate linear model analysis was used to evaluate pulmonary function effects of each pollutant in addition to determinants of indoor air pollution and meteorologic conditions. We found a significantly negative association of peak O(3) concentration on the day before spirometry with individual forced vital capacity and forced expiratory volume in 1 sec. The decrease in children's lung function can occur at peak hourly O(3) concentrations < 80 ppb. The slope of lung function decrease for Taiwanese children is approximately 1 mL/ppb for peak hourly O(3) exposure.

Adolescent↗
PubMed1999

Preliminary neuropsychological outcomes of angioplasty and stenting of extracranial cerebral arteries.

Preliminary evaluation of the neuropsychological status of three Chinese-speaking patients receiving angioplasty and stenting of extracranial cerebral arteries showed no significant decline in their performance on cognitive tasks measuring (1) memory function, verbal and nonverbal memory, (2) attention, and (3) cognitive processing speed. Although angioplasty and stenting of extracranial cerebral arteries did not appear associated with detrimental changes in the cognitive status of the two patients completing all cognitive tasks, their relation must be confirmed as a neuropsychologically safe measure for reducing the risk of stroke in Chinese with significant extracranial cerebral artery stenosis by a randomized controlled study with a much larger sample.

Aged↗
PubMed1999

Cytokines and apoptotic molecules in experimental melanin-protein induced uveitis (EMIU) and experimental autoimmune uveoretinitis (EAU).

The cytokine profile and occurrence of apoptosis during experimental melanin-protein induced uveitis (EMIU) were investigated and compared with that of experimental autoimmune uveoretinitis (EAU). EMIU or EAU was induced in Lewis rats. Eyes were collected at different time points after immunization. Cytokine mRNA expression was identified in the inflammatory cells in the uvea of EMIU rats; IL-2, IFN-gamma and IL-12 increased at the peak of the inflammation, and then tapered off as inflammation subsided. IL-4 and IL-10 increased at the peak of ocular inflammation, and persisted with inflammation resolved. Fas and FasL were expressed consistently in ocular resident cells of EMIU, but were elevated in EAU. In EAU, Bcl-2 expression showed a sharp peak in inflammatory cells but not in the resident cells. In EMIU, high levels of Bcl-2 were present and persisted in both ocular resident and inflammatory cells. Expression of Bax was relatively stable in both EAU and EMIU. Cellular DNA fragmentation was detected in the retinal glial cells of EAU and some inflammatory cells of EMIU. In EMIU, the dynamics of Th1 cytokines were consistent with the ocular inflammation, whereas persistent expression of Th2 cytokines was consistent with their known regulatory role. The continuous high expression of Bcl-2 and the high ratio of Bcl-2 to Bax in the eyes of EMIU may possibly contribute to prevention of ocular tissue damage, and of inflammatory cells from undergoing apoptosis, thus resulting in chronic recurrent inflammation.

Animals↗
PubMed1999

Oxidative bioactivation of the lactol prodrug of a lactone cyclooxygenase-2 inhibitor.

The lactol derivative of a lactone cyclooxygenase-2 inhibitor (DFU) was evaluated in vivo and in vitro for its potential suitability as a prodrug. DFU-lactol was found to be 10 to 20 times more soluble than DFU in a variety of aqueous vehicles. After administration of DFU-lactol at 20 mg kg-1 p.o. in rats, a Cmax of 7.5 microM DFU was reached in the plasma. After oral administration, the ED50s of DFU-lactol in the carrageenan-induced paw edema and lipopolysaccharide-induced pyresis assays in rats are comparable with the ED50s observed when dosing with DFU. Incubations of DFU-lactol with rat and human hepatocytes demonstrated that the oxidation of DFU-lactol can be mediated by liver enzymes and that a competing pathway is direct glucuronidation of the DFU-lactol hydroxyl group. Assays with subcellular fractions from rat liver indicated that most of the oxidation of DFU-lactol occurs in the cytosolic fraction and requires NAD(P)+. Human liver cytosol can also support the oxidation of DFU-lactol to DFU when NAD(P)+ is added to the incubations. Fractionation of human liver cytosolic proteins showed that at least three enzymes are capable of efficiently effecting the oxidation of DFU-lactol to DFU. Incubations with commercially available dehydrogenases suggest that alcohol and hydroxysteroid dehydrogenases are involved in this oxidative process. These data together suggest that lactols may represent useful prodrugs for lactone-containing drugs.

Animals↗
PubMed1999

Antepartum hemorrhage of unknown origin--what is its clinical significance?

BACKGROUND: Antepartum hemorrhage of unknown origin is a common antenatal complication, accounting for more than half of the cases of antepartum hemorrhage. Few investigators had reported the importance of this condition and the proper management. METHOD: The present study reviewed retrospectively 718 cases with singleton pregnancies diagnosed as having antepartum hemorrhage of unknown origin after 24 weeks from 1991 to 1996 and compared their pregnancy outcomes with controls who delivered during the same period of time as the study cases. Clinical and ultrasound examinations were performed in all recruited cases to exclude accidental hemorrhage, placenta previa or lower genital tract bleeding. RESULTS: Patients with antepartum hemorrhage of unknown origin ran a higher risk of spontaneous preterm labor (p<0.001). The birthweight, when adjusted for gestation, did not differ between the two groups. Labor induction rate and cesarean section rates were significantly higher in the antepartum hemorrhage group. The incidences of major antepartum complications and neonatal complications did not differ between the two groups. There were more babies with congenital abnormalities in the antepartum hemorrhage group (p<0.001) and perinatal mortality rate was also higher, though this difference was not statistically significant. CONCLUSION: The main fetal risks associated with antepartum hemorrhage of unknown origin is preterm labor and its subsequent fetal complications. A small but significant proportion of these pregnancies might be associated with fetal congenital abnormalities. Routine induction at term for this group of patients is of questionable value as adverse fetal outcomes are mostly associated with those that delivered prematurely, or with babies with congenital malformations. When gross fetal abnormalities could be reasonably excluded, labor induction at term should only be contemplated in the presence of other obstetric indications.

Adult↗
PubMed1999

Protective effect of the type IV phosphodiesterase inhibitor rolipram in EAU: protection is independent of IL-10-inducing activity.

PURPOSE: Experimental autoimmune uveoretinitis (EAU) is a cell-mediated model of retinal autoimmunity that is negatively regulated by interleukin (IL)-10. The antidepressant drug rolipram, a type IV phosphodiesterase inhibitor, enhances IL-10 production by monocyte/macrophages. The effect of rolipram on induction of EAU and its associated immunologic responses was investigated. METHODS: Mice were challenged for EAU induction by immunization with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP) or by adoptive transfer of uveitogenic T cells and were treated with rolipram. EAU severity and immunologic responses to IRBP were analyzed. In addition, the effect of rolipram added to the culture on antigen-driven responses of primed lymph node cells was tested. RESULTS: Rolipram treatment from days -1 to 7 after immunization (afferent phase) was not protective, but severity of EAU was reduced to 50% by treatment from days 8 to 16 after immunization or when EAU was induced by adoptive transfer (efferent phase). Antigen-specific proliferation and interferon (IFN)-gamma production ex vivo by lymph node cells of protected mice were not reduced. However, the addition of rolipram directly to the culture suppressed IRBP-driven proliferation and IFN-gamma production by primed lymph node cells. Freshly explanted lymph node cells of treated mice showed inhibition of IFN-gamma mRNA but no parallel enhancement of IL-10 mRNA by quantitative polymerase chain reaction. Rolipram inhibited EAU in IL-10 knockout mice equally well compared with controls and suppressed their primed lymph node cells in culture. CONCLUSIONS: Rolipram appears to inhibit the expansion and effector function of uveitogenic T cells, raising the possibility that it may be useful for treatment of established disease. Contrary to expectations based on in vitro studies, the protective effects in vivo appear to be independent of IL-10. The observation that suppression of antigen-specific responses is demonstrable only in the physical presence of the drug suggests that, in a clinical setting, continuous administration of rolipram might be needed to sustain its therapeutic effect.

Adoptive Transfer↗
PubMed1999

Mice deficient in inducible nitric oxide synthase are susceptible to experimental autoimmune uveoretinitis.

PURPOSE: Nitric oxide (NO) is an important mediator of inflammatory tissue damage. The present study addresses the question whether inducible nitric oxide synthase (iNOS), and consequently the ability to upregulate NO, is required to effect the pathogenesis of experimental autoimmune uveoretinitis (EAU) in mice. METHODS: Mice with a homologous disruption of the iNOS gene (iNOS KO) were evaluated for their ability to develop EAU and associated cellular responses after immunization with the interphotoreceptor retinoid-binding protein. EAU was determined by histopathology 21 days after uveitogenic immunization, and antigen-specific cellular responses were assessed by delayed type hypersensitivity and lymphocyte proliferation. RESULTS: iNOS knockout (iNOS KO) mice developed EAU with scores similar to wild-type mice and exhibited good cellular responses to the immunizing antigen. CONCLUSIONS: A functional iNOS gene is not necessary for EAU pathogenesis. Therefore, upregulation of NO is not required to mediate autoimmune tissue damage in the eye.

Animals↗
PubMed1999

Plasma concentrations of interferon-alpha in patients with liver cirrhosis: relationship to systemic and portal hemodynamics.

BACKGROUND: Nitric oxide (NO) plays an important role in the pathogenesis of the hyperdynamic circulation observed in portal hypertensive states. Interferon (IFN)-alpha can stimulate NO formation directly or indirectly via cytokines. However, IFN-alpha concentrations seem to increase or decrease in cirrhotic patients. This study investigated the plasma concentration of IFN-alpha in patients with cirrhosis and its relationship to systemic and portal hemodynamics. METHODS: Thirty-six patients with cirrhosis and 47 healthy controls had blood samples taken for the determination of plasma concentrations of IFN-alpha by enzyme-linked immunosorbent assay. Systemic and portal hemodynamics were measured in patients with cirrhosis on the same day of blood sampling using Swan-Ganz catheterization and the thermodilution technique. RESULTS: As compared with healthy subjects, patients with cirrhosis demonstrated a significantly higher IFN-alpha detectable rate (> 3 pg/ml, 14.9% vs 36.1%, p < 0.05). In cirrhotic patients, the IFN-alpha detectable rates were similar between those with and without decompensation, a hepatic venous pressure gradient greater than 12 mmHg, or the presence of large esophageal varices (p > 0.05). There was no significant difference in the systemic vascular resistance or hepatic venous pressure gradient between cirrhotic patients with and without a detectable plasma IFN-alpha concentration. CONCLUSIONS: Plasma IFN-alpha concentrations tended to increase in patients with cirrhosis. However, IFN-alpha concentrations do not play a role in the hyperdynamic circulation observed in patients with cirrhosis.

Adult↗
PubMed1999

Rofecoxib [Vioxx, MK-0966; 4-(4'-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles.

The discoveries that cyclooxygenase (COX)-2 is an inducible form of COX involved in inflammation and that COX-1 is the major isoform responsible for the production of prostaglandins (PGs) in the gastrointestinal tract have provided a rationale for the development of specific COX-2 inhibitors as a new class of anti-inflammatory agents with improved gastrointestinal tolerability. In the present study, the preclinical pharmacological and biochemical profiles of rofecoxib [Vioxx, also known as MK-0966, 4-(4'-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone], an orally active COX-2 inhibitor, are described. Rofecoxib is a potent inhibitor of the COX-2-dependent production of PGE(2) in human osteosarcoma cells (IC(50) = 26 +/- 10 nM) and Chinese hamster ovary cells expressing human COX-2 (IC(50) = 18 +/- 7 nM) with a 1000-fold selectivity for the inhibition of COX-2 compared with the inhibition of COX-1 activity (IC(50) > 50 microM in U937 cells and IC(50) > 15 microM in Chinese hamster ovary cells expressing human COX-1). Rofecoxib is a time-dependent inhibitor of purified human recombinant COX-2 (IC(50) = 0.34 microM) but caused inhibition of purified human COX-1 in a non-time-dependent manner that could only be observed at a very low substrate concentration (IC(50) = 26 microM at 0.1 microM arachidonic acid concentration). In an in vitro human whole blood assay, rofecoxib selectively inhibited lipopolysaccharide-induced, COX-2-derived PGE(2) synthesis with an IC(50) value of 0.53 +/- 0.02 microM compared with an IC(50) value of 18.8 +/- 0.9 microM for the inhibition of COX-1-derived thromboxane B(2) synthesis after blood coagulation. Using the ratio of the COX-1 IC(50) values over the COX-2 IC(50) values in the human whole blood assay, selectivity ratios for the inhibition of COX-2 of 36, 6.6, 2, 3, and 0.4 were obtained for rofecoxib, celecoxib, meloxicam, diclofenac, and indomethacin, respectively. In several in vivo rodent models, rofecoxib is a potent inhibitor of carrageenan-induced paw edema (ID(50) = 1.5 mg/kg), carrageenan-induced paw hyperalgesia (ID(50) = 1.0 mg/kg), lipopolysaccharide-induced pyresis (ID(50) = 0.24 mg/kg), and adjuvant-induced arthritis (ID(50) = 0.74 mg/kg/day). Rofecoxib also has a protective effect on adjuvant-induced destruction of cartilage and bone structures in rats. In a (51)Cr excretion assay for detection of gastrointestinal integrity in either rats or squirrel monkeys, rofecoxib has no effect at doses up to 200 mg/kg/day for 5 days. Rofecoxib is a novel COX-2 inhibitor with a biochemical and pharmacological profile clearly distinct from that of current nonsteroidal anti-inflammatory drugs and represents a new therapeutic class of anti-inflammatory agents for the treatment of the symptoms of osteoarthritis and rheumatoid arthritis with improved gastrointestinal tolerability.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1999

Psychosocial risk factors of teenage pregnancy in eastern Taiwan.

BACKGROUND: Teenage pregnancy is a growing worldwide problem, associated with adolescents' social and health problems and poor perinatal outcome. This study was conducted to investigate psychosocial factors predisposing to the high teenage pregnancy rate in Hualien, eastern Taiwan. METHODS: A regional hospital-based study was conducted with a retrospective analysis of hospital records and questionnaires to collect personal and family data regarding the perinatal outcome of 100 pregnant teenagers and 100 pregnant adults, who had normal deliveries at the Buddhist Tzu-Chi General Hospital between 1994 and 1995. RESULTS: A significantly higher percentage of teenage mothers were of aboriginal origin than adult mothers (63% vs 25%; p < 0.05) and lived in rural areas (80% vs 19%; p < 0.05). There was also a higher incidence of late antenatal care (31% vs 11%; p < 0.05) drinking (36% vs 9%; p < 0.05) and a greater history of smoking (34% vs 7%; p < 0.05) among teenage mothers. About 86% of teenage mothers did not use any contraception. The preterm birth rate was not significantly higher in the adult group, but teenage mothers tended to have significantly lower birth weight infants (19% vs 9%; p < 0.05) and a decreased incidence of cesarean section (19% vs 33%; p < 0.05). About 20% of the teenage mothers had their first coitus before the age of 13, while none of the adult mothers had sexual coitus before the age of 13. CONCLUSIONS: In this hospital-based study, teenage mothers tended to be of aboriginal origin, lived in rural areas, had early sexual exposure without contraception, had drinking and smoking habits, were late seeking antenatal care and gave birth to low birth weight infants.

Adolescent↗