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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 217 records · Page 12Linked to original sources

Transcervical embryoscopic diagnosis of conjoined twins in a ten-week missed abortion.

Embryoscopic diagnosis of conjoined twins presenting with a missed abortion has never been reported. The morphological and pathological examinations, and the exact time of death in the conceptus of a missed abortion are seldom clearly delineated. The newly developed field of embryoscopy has created a new frontier in early embryonic/fetal visualization and is able to confirm the sonographic diagnosis. In this report, we used a transcervical endoscope to verify conjoined twins (thoraco-omphalopagus) in a 10-week missed abortion. Based on the size and the external features of the dead embryo, which exhibited developmental arrest at nine weeks and three days of menstrual age, we estimated that the embryo had died four days before examination. The whole procedure proceeded smoothly without any immediate complications.

Abortion, Missed↗

Recurrent spontaneous bacterial empyema in cirrhosis: a case report.

Spontaneous bacterial empyema occurs in about 0.4% of cirrhotic patients, but recurrent attack has rarely been reported. Herein we report a case of repeat episodes of spontaneous bacterial empyema. The patient presented with fever, shortness of breath and three episodes of spontaneous bacterial empyema (accompanied by septic shock in two episodes) within six months. Chest roentgenography showed massive right-side pleural effusion. Thoracentesis yielded pleural effusion containing a neutrophil count of more than 500/microliter. A blood culture grew non-O1 Vibrio cholerae in one episode and the pleural effusion culture grew Aeromonas hydrophila. A chest-tube was inserted during the latest episode due to a low pH and glucose concentration in the pleural fluid. The patient recovered well after medical treatment. The etiology, diagnosis and management of spontaneous bacterial empyema are discussed.

4-Quinolones↗

The obstructive sleep apnoea syndrome--experience of a referral centre.

OBJECTIVE: The aims of this study were: (i) to document the presence and severity of obstructive sleep apnoea (OSA) in patients who complained of heavy snoring and other symptoms suggestive of the OSA syndrome; (ii) to examine the correlation between the clinical and polygraphic findings, and (iii) to document the efficacy and compliance of nasal continuous positive airway pressure (CPAP) among these Asian snorers with OSA. METHODS: We analysed our clinical and nocturnal polysomnographic data between January 1986 and December 1995 for physician-referred patients who had complained of snoring and other symptoms suggestive of OSA. RESULTS: A total of 277 diagnostic studies were performed of which 145 (52%) were positive to OSA. For studies performed in the last 2 years (n = 125), 72 of the 125 were positive for OSA. Anthropometric data was not discriminative between the OSA positive snorers and the OSA negative snorers. We found that hypertension and choking were the most significantly related to OSA, conferring a 7 and 4 times relative risk respectively. Nasal CPAP eliminated snoring, apnoeas and oxygen desaturations completely in almost all cases and there were only minor mask-related side effects. CONCLUSION: OSA may not be uncommon among Asian snorers. Of the major traits for OSA risk among our local population, a history of hypertension and reports of nocturnal choking were the most significantly related. We have also shown that nasal CPAP is safe and effective among our local snorers and should be considered a first-line treatment for OSA.

Adult↗

One-week low-dose triple therapy is effective in treating Helicobacter pylori-infected patients with bleeding peptic ulcers.

Proton pump inhibitor (PPI)-based triple therapy, which combines a PPI and two antibiotics, is highly effective in eradicating Helicobacter pylori infection in peptic ulcer patients, even if given for only 1 week. However, the application of this regimen in patients with bleeding ulcers has not been adequately investigated. We studied the effectiveness of triple therapy in treating 122 patients with proven H. pylori infection, and bleeding stigmata on endoscopy; 97 had duodenal ulcer (DU), 15 had gastric ulcer (GU), and 10 had both types of ulcers. A regimen of omeprazole (20 mg), metronidazole (500 mg), and clarithromycin (250 mg) twice daily was administered for 1 week as soon as the patient could eat normally after bleeding, followed by omeprazole (20 mg) daily for 3 additional weeks. Follow-up endoscopy and 13C-urea breath tests (UBTs) were performed at least 4 weeks after triple therapy. A total of 104 patients completed the study, 83 with DU, 12 with GU, and nine with both. The overall ulcer healing rate was 97.1% and the eradication rate was 91.3%. Patients with and without H. pylori eradication did not differ significantly in terms of age, gender, UBT titer, units of blood transfused, or interval between endoscopy and the beginning of triple therapy. We conclude that 1-week low-dose PPI-based triple therapy is effective in eradicating H. pylori infection in patients with bleeding peptic ulcers. When followed by 3 weeks of additional PPI treatment, a satisfactory ulcer healing rate can also be achieved.

Adult↗

VOC concentration in Taiwan's household drinking water.

The objective of this study is to analyze volatile organic compound (VOC) concentrations in Taiwan's drinking water supply. Focusing on Taiwan's three major metropolitan areas--Taipei, Taichung and Kaohsiung (in the north, middle and south, respectively)--171 samples were taken from tap water and 68 from boiled water. Tests showed VOC concentrations were highest in Kaohsiung. This is due to different water sources and methods of treatment. Except for bromoform, trihalomethane (THM) concentrations were highest. Detection rates of toluene and 1,2-dichloroethane were slightly higher than other VOC compounds. VOC concentrations decreased significantly after water was boiled. THMs had a removal rate from 61% to 82%. The authors conclude that the three metropolitan areas contain significantly different levels of VOCs and that boiling can significantly reduce the presence of VOCs. Other sources of pollution that contaminate drinking water such as industrial plants and gas stations must be further investigated.

Environmental Exposure↗

Substituted (pyridylmethoxy)naphthalenes as potent and orally active 5-lipoxygenase inhibitors; synthesis, biological profile, and pharmacokinetics of L-739,010.

Dioxabicyclooctanyl naphthalenenitriles have been reported as a class of potent and nonredox 5-lipoxygenase (5-LO) inhibitors. These bicyclo derivatives were shown to be metabolically more stable than their tetrahydropyranyl counterparts but were not well orally absorbed. Replacement of the phenyl ring in the naphthalenenitrile 1 by a pyridine ring leads to the potent and orally absorbed inhibitor 3g (L-739,010, 2-cyano-4-(3-furyl)-7-[[6-[3-(3-hydroxy-6,8-dioxabicyclo[3.2.1] octanyl)]-2-pyridyl]methoxy]naphthalene). Compound 3g inhibits 5-HPETE production by human 5-LO and LTB4 biosynthesis by human PMN leukocytes and human whole blood (IC50S of 20, 1.6, and 42 nM, respectively). Derivative 3g is orally active in the rat pleurisy model (inhibition of LTB4, ED50 = 0.3 mg/kg) and in the anesthetized dog model (inhibition of ex vivo whole blood LTB4 and urinary LTE4, ED50 = 0.45 and 0.23 microgram/kg/min, respectively, i.v. infusion). In addition, 3g shows excellent functional activity against ovalbumin-induced dyspnea in rats (60% inhibition at 0.5 mg/kg, 4 h pretreatment) and Ascaris-induced bronchoconstriction in conscious sheep (50% and > 85% inhibition in early and late phases, respectively at 2.5 micrograms/kg/min, i.v. infusion) and, more particularly in the conscious antigen sensitive squirrel monkey model (53% inhibition of the increase in RL and 76% in the decrease of Cdyn, at 0.1 mg/kg, po). In rats and dogs, 3g presents excellent pharmacokinetics (estimated half-lives of 5 and 16 h, respectively) and bioavailabilities (26% and 73% when dosed as its hydrochloride salt at doses of 20 and 10 mg/kg, respectively, in methocel suspension). Based on its overall biological profile, compound 3g has been selected for preclinical animal toxicity studies.

Animals↗

Septic tenosynovitis and focal osteomyelitis of the lateral proximal sesamoid bone in a thoroughbred gelding.

Chronic septic tenosynovitis with concurrent, associated focal osteomyelitis of the lateral proximal sesamoid bone was diagnosed in a seven-year-old thoroughbred gelding. Surgical management of this case consisted of open annular ligament desmotomy and curettage of the affected sesamoid. Following lavage of the digital sheath the incisional wound was closed but a 2 cm gap was left distally to allow for postoperative open drainage. The distal limb was bandaged and the horse treated with antibiotics and non-steroidal anti-inflammatories. Sepsis resolved and the horse made a gradual return to full work.

Animals↗

Blood-retinal barrier (BRB) breakdown in experimental autoimmune uveoretinitis: comparison with vascular endothelial growth factor, tumor necrosis factor alpha, and interleukin-1beta-mediated breakdown.

Experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by immunization with S-antigen is a model of human uveitis. By using immunocytochemical staining for albumin, relatively minor blood-retinal barrier (BRB) breakdown was initially shown in the peripheral retina 8 days after immunization and in the posterior retina by 10 days. Albumin extravasation appeared to occur by opening of the retinal vascular endothelial (RVE) and the retinal pigmented epithelial (RPE) tight junctions, by transendothelial vesicular transport, and by permeating damaged RVE cells. Each of three anti-inflammatory agents reduced or delayed autoimmune-mediated cell destruction but did not eliminate any particular route of extravasation. Vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF alpha), and interleukin-1beta (IL-1beta) are intimately associated with the development of EAU and are capable of causing BRB dysfunction. A high percentage of RVE tight junctions appeared open ultrastructurally after intravitreal injection of VEGF (26.7%), TNF alpha (35.6%), or IL-1beta (22.1%) compared with saline-injected control (11.4%) or normal, untreated rabbits (4.1%). Heat treatment abolished the effect of IL-1beta on the BRB but only partially reduced the effect of VEGF. By 24 hr after injection, the effect of TNF alpha had reversed, but that of IL-1beta had not; VEGF-mediated BRB dysfunction was partially reversible. In addition, albumin-filled vesicle-like structures were seen in the RVE cytoplasm following treatment with each mediator. This study shows that VEGF, TNF alpha, and IL-1beta each cause BRB breakdown by opening tight junctions between RVE cells and possibly by increasing transendothelial vesicular transport. Each of these agents may contribute to BRB breakdown in EAU and in patients with uveitis.

Albumins↗

Genetic susceptibility to experimental autoimmune uveitis involves more than a predisposition to generate a T helper-1-like or a T helper-2-like response.

This study examines whether genetic susceptibility vs resistance to experimental autoimmune uveoretinitis (EAU) in mice is associated with dominant type 1 vs type 2 cytokine response profiles. Mice from six strains were immunized with the uveitogenic retinal Ag IRBP. EAU was evaluated by histopathology. As judged by disease scores, three of the strains were susceptible, one was minimally susceptible, and two were resistant. Ag-specific type 1 vs type 2 cytokine responses (protein and/or mRNA) in draining lymph node cells, and IgG2a vs IgG1 Ab isotypes to IRBP, were measured as indicators of Th1-like vs Th2-like responses, respectively. The three susceptible strains (B10.A, C57BL/10, and BALB/k) showed a dominant Th1-like response profile characterized by high IFN-gamma and IL-12p40 (but not IL-4) responses, and a predominance of IgG2a Abs. The minimally susceptible strain (A/J) had an IFN-gamma response detectable only at the mRNA level, but produced predominantly IgG2a Abs. One of the two resistant strains (BALB/c) showed a characteristic Th2-like response with dominant Ag-specific IL-4 and IL-10 responses but no IFN-gamma, and predominantly IgG1 Abs. However, the other resistant strain (AKR) did not show a Th2-dominated response pattern, in that it had low, or no, IL-4 and IL-10 responses, and made predominantly IgG2a Abs to IRBP. These results suggest that whereas a Th1 response is required for susceptibility, resistance is not dependent on a Th2 response pattern. We suggest that regulatory influences other than skewing the response toward the Th2 pathway may be equally effective at conferring genetic resistance to EAU.

Animals↗

IFN-gamma-deficient mice develop experimental autoimmune uveitis in the context of a deviant effector response.

Experimental autoimmune uveitis (EAU) is a T cell-mediated disease that targets the neural retina and serves as a model of human uveitis. Uveitogenic effector T cells have a Th1-like phenotype (high IFN-gamma, low IL-4), and genetic susceptibility to EAU is associated with an elevated Th1 response. Here we investigate whether the ability to produce IFN-gamma is necessary for the development of EAU by immunizing IFN-gamma-deficient (GKO) mice with the uveitogenic protein interphotoreceptor retinoid binding protein (IRBP) and characterize the associated immunologic responses. GKO mice developed EAU comparable in severity and incidence to that of their wild-type littermates. However, the cytokine profile in their uveitic eyes as well as the cytokines produced by primed lymph node cells in response to IRBP showed a distinct profile: undiminished TNF-alpha and elevated IL-5, IL-6, IL-10, and lymphotoxin (but not IL-4) responses. The inflammatory infiltrate in GKO eyes contained an excess of granulocytes and IL-5- and IL-6-producing cells, but uveitic GKO mice did not up-regulate inducible nitric oxide synthase. GKOs had enhanced lymphocyte proliferation and delayed-type hypersensitivity responses to IRBP. Histology of the delayed-type hypersensitivity lesion in GKO had superimposed elements of an allergic-like response. Anti-IRBP Ab isotypes of GKO mice showed a reduction of IgG2a, but no enhancement of IgG1. Comparison of responses in +/+ and +/- wild-type mice revealed some limited evidence of a gene-dose effect. We conclude that IFN-gamma is not required for priming of pathogenic T cells or for effecting the retinal damage and photoreceptor loss typical of EAU. However, what appears to be a grossly similar disease is caused in the GKO by a deviant type of effector response.

Animals↗

A selective inhibitor of cyclooxygenase-2 reverses endotoxin-induced pyretic responses in non-human primates.

The anti-pyretic effect of a selective cyclooxygenase-2 inhibitor, DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furano ne), was examined in conscious, un-restrained squirrel monkeys (Saimiri sciureus) using a radio telemetric system. Injection of bacterial endotoxin (lipopolysaccharide, 6 microg kg(-1), i.v.) in squirrel monkeys caused a gradual increase in core body temperature reaching a plateau of 2.07 +/- 0.17 degrees C above baseline at 2 h post-injection. Oral administration of DFU (1 mg kg(-1)) reduced, and DFU (3 mg kg(-1)) completely reversed the lipopolysaccharide-induced pyretic responses. The onset of action of DFU (about 30 min) is in good agreement with the pharmacokinetic profile of this compound in squirrel monkeys. The effect of DFU is comparable to that of a conventional non-selective non-steroidal anti-inflammatory drug (NSAID), diclofenac (3 mg kg(-1)). Since the plasma levels achieved for DFU at the dose employed in the present study are below the threshold required for inhibition of cyclooxygenase-1, it is concluded that the anti-pyretic effect of DFU can be attributed predominantly to an inhibitory action on cyclooxygenase-2. Thus, lipopolysaccharide-induced pyresis in squirrel monkeys can be used as a model for evaluation of anti-pyretic activity of cyclooxygenase inhibitors.

Analgesics, Non-Narcotic↗

Treatment of a keratoma in a Clydesdale horse.

A keratoma was diagnosed in a six-year-old Clydesdale gelding with recurrent 'pus in the foot'. The keratoma was excised through an inverted 'V' dorsal wall hoof resection up to 2 cm distal to the coronary band, the foot was bandaged and shod, and the horse treated with antibiotics and phenylbutazone. The dorsal hoof wall regrew completely and the horse gradually returned to full work.

Animals↗

Humanized antibodies against the alpha-chain of the IL-2 receptor and against the beta-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases.

We studied the efficacy and tolerance of humanized Ab interfering with the signal of the IL-2 and IL-15 receptors in a primate model of experimental autoimmune uveoretinitis. The inhibitory effects of humanized anti-Tac (HAT), an anti-IL-2R alpha-chain Ab, and HuMik beta1, an Ab directed at the beta-chain shared by the receptors of IL-2 and IL-15, were tested in culture on the proliferative response of monkey Con A-blast lymphocytes stimulated with IL-2 or IL-15. Uveitis was induced in cynomolgus monkeys by immunization with human recombinant retinal S-antigen. Treatment was initiated at the first sign of disease and consisted of HAT and HuMik beta1, alone or in combination, or vehicle control given by i.v. injection twice a week for 4 wk. Disease was evaluated by ocular funduscopy. The results in culture showed a significant dose-dependent inhibition of the IL-2-driven proliferation of lymphocytes by HAT. HuMik beta1 alone was ineffective against IL-2 stimulation, but had a marked potentiating effect in combination with HAT, independent of IL-15 signaling. IL-15-driven proliferation was inhibited by HuMik beta1, but not by HAT alone or in combination. In monkeys, experimental autoimmune uveoretinitis evolution was significantly inhibited by HAT treatment. HuMik beta1 alone had no effect on the disease. However, when used in combination, the two Ab markedly reduced the severity of ocular inflammation. The Ab were well tolerated. Only three monkeys, treated with HAT alone, made an Ab response against the injected Ab.

Animals↗

Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma.

BACKGROUND: Diagnosis of primary central nervous system lymphoma (PCNSL) is usually made by identifying malignant lymphocytes in the brain, cerebrospinal fluid (CSF), or vitreous. However, these cells are few and friable, and misdiagnosis can occur, even in properly prepared specimens. Recent data suggest that levels of interleukin 10 (IL-10) are elevated in the serum and vitreous of patients with non-Hodgkin lymphoma; levels of interleukin 6 (IL-6) are elevated in the vitreous of patients with intraocular inflammation unrelated to a malignant neoplasm. We investigated whether PCNSL involving the vitreous or CSF is associated with elevated ratios of IL-10 to IL-6. PATIENTS: Vitreous specimens were obtained from 5 patients with PCNSL involving the eye and from 13 control patients with intraocular inflammation not related to a malignant neoplasm; CSF specimens were obtained from 11 patients with PCNSL. RESULTS: Levels of IL-10 exceeded those of IL-6 in all 5 patients with intraocular lymphoma but in none of the 13 patients with uveitis (P < .001). In patients with PCNSL, levels of IL-10 exceeded those of IL-6 in 6 of 11 CSF samples with malignant cells compared with 7 of 53 samples without malignant cells (P = .01). The calculated odds ratio (OR) suggests that the risk for malignant involvement of the CSF is about 8 times higher when IL-10 levels exceed IL-6 levels. METHODS: Levels of IL-10 and IL-6 were determined by enzyme-linked immunosorbent assay in both vitreous and CSF specimens. CONCLUSIONS: The occurrence of PCNSL in the eye was strongly associated with elevated vitreous levels of IL-10 relative to levels of IL-6. Moreover, among patients with diagnosed PCNSL, malignant cells were significantly more likely to be present in CSF when levels of IL-10 exceeded those of IL-6.

Central Nervous System Neoplasms↗

Ganciclovir implant exchange. Timing, surgical procedure, and complications.

BACKGROUND: The ganciclovir implant is effective for the treatment of cytomegalovirus (CMV) retinitis. The device eventually runs out of drug, however, and must be replaced. We report our experience with exchanging ganciclovir implants during the course of a randomized clinical trial. METHODS: During our study, patients with newly diagnosed peripheral CMV retinitis were treated with a ganciclovir implant. The implant was scheduled for exchange at 32 weeks. It was exchanged earlier if progression of CMV retinitis occurred. Patient examinations and standard fundus photography were performed at 2-week intervals after the exchange procedure. RESULTS: Twenty-six exchange procedures were performed. Twenty-two eyes in 15 patients received a second implant and 4 eyes in 4 patients later received a third implant. Cytomegalovirus retinitis was rendered or maintained inactive in 22 of 23 cases with more than 1 month of follow-up after the second or third implants. Complications after the second implant procedure included transient vitreous hemorrhage in 5 eyes, postoperative inflammation in 1 eye, and retinal detachment in 1 eye. Median visual acuity returned to 20/25 by 28 days and to 20/20 by 42 days. Complications after the third implant procedure included dense vitreous hemorrhage in 3 of 4 eyes. Median survival time after a second implant procedure was 89 days. CONCLUSIONS: The initial ganciclovir implant exchange procedure is well tolerated with continued long-term control of CMV retinitis. Multiple reentries through the same wound may be associated with an increased risk for vitreous hemorrhage.

Antiviral Agents↗

Apoptosis in patients with posterior uveitis.

BACKGROUND: Apoptosis plays a part in the pathogenesis of autoimmune diseases. OBJECTIVE: To investigate the expression of apoptotic markers in the eyes of patients with uveitis. METHODS: With the use of immunohistochemical and in situ apoptotic detection techniques, apoptotic molecules (Fas or Fas ligand [FasL]) and nuclear DNA fragmentation were examined in 8 enucleated eyes with Behçet's disease (1), sarcoidosis (1), subretinal fibrosis and uveitis (1), sympathetic ophthalmia (4), and the Vogt-Koyanagi-Harada syndrome (1); in 5 chorioretinal biopsy specimens with acute retinal necrosis (2), multifocal choroiditis (1), sarcoidosis (1), and subretinal fibrosis and uveitis (1); and in 3 normal control eyes. RESULTS: Fas and FasL were constitutively expressed in the normal human retina, but they were expressed much less in the choroid. Increased expression of Fas and FasL was found in the retina, chorioretinal scar, and choroidal granulomas in uveitic eyes. However, Fas and FasL expression was absent in the biopsy specimens with acute retinal necrosis, and little Fas or FasL was noted on infiltrating lymphocytes. DNA fragmentation was also identified in eyes with chorioretinal scar and gliosis. CONCLUSIONS: Apoptosis occurs in uveitic eyes and may play a regulatory role in limiting ocular inflammation. In uveitic eyes, a dysregulation of the Fas-FasL apoptotic pathway may lead to gliosis and fibrosis.

Adolescent↗

Blocking both E-selectin and P-selectin inhibits endotoxin-induced leukocyte infiltration into the eye.

The initial contact between leukocytes and the vascular endothelium at sites of inflammation is mediated by selectins. The purpose of this study was to investigate the role of the two selectins expressed on the vascular endothelium, E-selectin and P-selectin, in the pathogenesis of endotoxin-induced uveitis. Endotoxin-induced uveitis was produced in female C3H/HeN mice using Salmonella typhimurium endotoxin injected into one hind footpad. At the time of endotoxin injection mice were treated with an intraperitoneal injection of a monoclonal antibody against E-selectin or P-selectin, a combination of both anti-selectin antibodies, or isotype-matched control antibodies. In a second set of experiments, antibody treatment was administered 6 hr after endotoxin injection, when inflammatory cells are already entering the eye. Ocular inflammation was graded histologically by a masked observer. When administered at the time of endotoxin injection, anti-P-selectin antibody decreased ocular inflammation by 37% compared to control animals (P = 0.05). There was no statistical decrease in ocular inflammation in animals treated with anti-E-selectin antibody. The combination of anti-P-selectin and anti-E-selectin antibodies decreased infiltrating inflammatory cells by 61% (P < 0.01). When treatment was delayed until 6 hr after endotoxin injection, the combination of anti-P-selectin and anti-E-selectin antibodies again decreased ocular inflammation by 60% (P < 0.01). Immunohistochemical staining showed decreased ICAM-1 expression in the eyes of animals treated with the combination of anti-P-and anti-E-selectin antibodies. Blocking both P-selectin and E-selectin resulted in a significant decrease in endotoxin-induced intraocular inflammation.

Animals↗