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Biomedical subjects

R Yung

Publications and source records attributed to R Yung.

At least 19 recordsLinked to original sources
PubMed2006

Optimising antimicrobial prescription in hospitals by introducing an antimicrobial stewardship programme in Hong Kong: consensus statement.

OBJECTIVE: To discuss the implementation of an 'antimicrobial stewardship programme' as a means to improve the quality of antimicrobial use in a hospital setting in Hong Kong. PARTICIPANTS: Consensus working group on 'antimicrobial stewardship programme', The Scientific Committee on Infection Control, Centre for Health Protection, Department of Health, comprised 11 experts. The remit of the working group was to discuss the rationale and requirement for optimising antimicrobial prescriptions in hospitals by the introduction of an 'antimicrobial stewardship programme'. EVIDENCE: PubMed articles, national and international guidelines, and abstracts of international meetings published between January 2000 and December 2004 on programmes for improving the use of antimicrobials in hospitals. Only English medical literature was reviewed. CONSENSUS PROCESS: Data search was performed independently by three members of the working group. They met on three occasions before the meeting to discuss all collected articles. A final draft was circulated to the working group before a meeting on 3 January 2005. Five commonly asked questions about an 'antimicrobial stewardship programme' were selected for discussion by the participants. Published information on the rationale, components, outcome measures, advantages, and disadvantages of the programme was reviewed. Recent unpublished data from local studies of an 'antimicrobial stewardship programme' were also discussed. The timing, potential problems, and practical issues involved in the implementation of an 'antimicrobial stewardship programme' in Hong Kong were then considered. The consensus statement was circulated to and approved by all participants. CONCLUSION: The continuous indiscriminate and excessive use of antimicrobial agents promotes the emergence of antibiotic-resistant organisms. Antimicrobial resistance substantially raises already-rising health care costs and increases patient morbidity and mortality. Pattern of prescriptions in hospitals can be improved through the implementation of an 'antimicrobial stewardship programme'. A 'universal' and 'continuous' 'antimicrobial stewardship programme' should now be established in Hong Kong hospitals.

Anti-Infective Agents↗
PubMed2005

Candida tropicalis arthritis of the knee in a patient with acute lymphoblastic leukaemia: successful treatment with caspofungin.

Candida arthritis in patients with a haematological malignancy is rare. We report a case of Candida tropicalis arthritis of the knee that occurred in a patient with acute lymphoblastic leukaemia during the recovery phase of post-chemotherapy neutropenia. Although the Candida tropicalis isolates from synovial fluid and synovial tissue were sensitive to fluconazole in vitro, a 6-week course of oral treatment failed to produce clinical improvement. The arthritis resolved after 7 weeks of combination therapy with caspofungin, a new echinocandin class of antifungal agent that acts primarily on the cell wall. Eleven other reports of Candida arthritis in patients with a haematological malignancy were reviewed.

Antifungal Agents↗
PubMed2001

Unexpected effects of a heterozygous dnmt1 null mutation on age-dependent DNA hypomethylation and autoimmunity.

DNA methylation modifies gene expression. Methylation patterns are established during ontogeny, but they change with aging, usually with a net decrease in methylation. The significance of this change in T cells is unknown, but it could contribute to autoimmunity, senescence, or both. We examined the effects of a null mutation in DNA methyltransferase 1 (Dnmt1), a gene maintaining DNA methylation patterns, on immune aging. Whereas aged control mice developed hypomethylated DNA, autoimmunity, and signs of immune senescence as predicted, the knockout mice surprisingly increased DNA methylation and developed signs of autoimmunity and senescence more slowly. To identify potential mechanisms, we compared transcripts of DNA methyltransferase and methylcytosine binding protein family members in control and knockout mice. MeCP2, a methylcytosine binding protein involved in gene suppression and chromatin inactivation, was the only transcript differentially expressed between old knockout mice and controls, and thus it is a candidate for a gene product mediating these effects.

Aging↗
PubMed2001

Autoreactive murine Th1 and Th2 cells kill syngeneic macrophages and induce autoantibodies.

D10 cells, a cloned Th2 line, become autoreactive following treatment with DNA methylation inhibitors like 5-azacytidine (5-azaC), and induce anti-DNA antibodies if injected into unirradiated syngenic mice. The mechanism by which the autoreactive cells break tolerance is unknown. To further define effector functions required, we asked if 5-azaC-treated Th1 cells could also induce autoimmunity. AE7 cells, a cloned Th1 line, were treated with 5-azaC and shown to become autoreactive and induce anti-DNA antibodies in vivo. Comparison of effector mechanisms demonstrated that the two cell lines secreted a distinct repertoire of cytokines, and that only killing of syngeneic Mø was common to both AE7 and D10 cells. This suggests that Mø killing may be an early step in the induction of anti-DNA antibodies, providing antigenic nucleosomes and decreasing clearance of apoptotic material. Secretion of cytokines promoting B cell differentiation may play a role, but no one cytokine is required.

Animals↗
PubMed2000

SETA: a novel SH3 domain-containing adapter molecule associated with malignancy in astrocytes.

Differential display polymerase chain reaction analysis was used to compare five differentiation states of the O-2A progenitor-like cell line CG4: progenitor cells and cells at 12 h or 4 days after the induction of differentiation into oligodendrocytes or astrocytes. This led to the identification of 52 sequence tags that were expressed differentially with cellular phenotype. One sequence was upregulated during differentiation of CG4 cells and represented a novel gene that we named SETA (SH3 domain-containing gene expressed in tumorigenic astrocytes). This gene encodes an SH3 domain-containing adapter protein with sequence similarity to the CD2AP (CD2 adapter protein) and CMS (Cas ligand with multiple Src homology) genes. SETA mRNA was expressed at high levels in the developing rat brain but was barely detectable in the normal adult rat or human brain. However, SETA mRNA was found in approximately one half of the human gliomas tested, including astrocytomas grades II, III, and IV, as well as oligodendrogliomas, mixed oligoastrocytomas, and human glioma-derived cell lines. A rat glioma generated by treatment with the alkylating carcinogen ethylnitrosourea on postnatal day 1 and a derived cell line also expressed SETA mRNA. Furthermore, in an in vitro model of astrocytoma progression based on p53-/- astrocytes, expression of SETA was restricted to cells that are tumorigenic.

Animals↗
PubMed2000

Overview of interleukin-2 inhalation therapy.

PURPOSE: Locoregional administration of interleukin (IL)-2, which acts physiologically as a local hormone, is an effective therapeutic modality. Diverse preclinical and clinical models have described methods of administration that expose tumor tissues to continuously high levels of cytokines. Regional administration of IL-2 that does not raise intravascular IL-2 levels induces local and systemic immunomodulation and produces objective local tumor responses. Most importantly, regional therapy is much less toxic than systemic IL-2 therapy. PATIENTS AND METHODS: We review clinical experiences using inhaled IL-2 therapy for the treatment of pulmonary metastases in roughly 300 patients with a variety of primary tumors. This includes our own 10-year single-institution experience with inhaled IL-2 therapy in the treatment of 188 metastatic renal cell carcinoma patients with progressive pulmonary metastases. Patients in our clinic are treated with 18 to 36 million IU of recombinant IL-2, administered 90% by inhalation and 10% subcutaneously, until disease progression. A variety of doses and schedules of inhaled IL-2 have been investigated alone and in combination with systemic therapies. RESULTS: Inhalation of IL-2 has been reported to prevent progression of pulmonary and mediastinal metastases of metastatic renal cell carcinoma, breast and ovarian carcinoma, and melanoma. Inhaled IL-2 alone is well tolerated; a dose-dependent cough is the major adverse event. A significant dose-dependent increase in lymphocytes and eosinophils has been observed in bronchoalveolar lavage in patients and animals. Dose and schedule can influence outcome. In a phase I trial using inhaled IL-2 alone in patients with a variety of primary malignancies, once-daily inhalation of IL-2 at doses up to 15 million IU/m2 was well tolerated but did not result in prolonged stabilization of pulmonary disease. In a multidose phase I trial, using 5-times-daily inhalation of natural IL-2, pulmonary lesions in three of 14 (21%) metastatic renal cell carcinoma patients responded, and a similar multicenter trial demonstrated a 29% response rate. Among 188 metastatic renal cell carcinoma patients treated with inhaled recombinant IL-2 at the Clinic Eppendorf, progression of pulmonary metastases was prevented in 68% of patients for a median duration of 7 months, and overall survival was significantly improved compared with expected survival (Elson's risk analysis; 17.2 vs 5.3 mo). All patients, including high-risk patients, appeared to benefit. Encouraging results have also been reported in patients with metastatic melanoma and gynecologic tumors when inhaled IL-2 was used as second-line therapy to treat pulmonary metastases. CONCLUSIONS: The efficacy of inhaled IL-2, alone or in combination with systemic immunotherapy, immunochemotherapy, or chemotherapy, has been documented in a variety of malignancies. All reports confirm low toxicity, thus providing important quality-of-life benefits. Moreover, patients not eligible for systemic IL-2 therapy may be treated with inhalation therapy.

Administration, Inhalation↗
PubMed1999

Analysis of human peripheral blood T cells and single-cell-derived T cell clones uncovers extensive clonal CpG island methylation heterogeneity throughout the genome.

Methylation of cytosine residues in CpG dinucleotides is generally associated with silencing of gene expression. DNA methylation, as a somatic event, has the potential of diversifying gene expression in individual cells of the same lineage. There is little quantitative data available concerning the extent of methylation heterogeneity in individual cells across the genome. T cells from the peripheral blood can be grown as single-cell-derived clones and can be analyzed with respect to their DNA methylation patterns by restriction landmark genomic scanning. The use of the methylation-sensitive enzyme NotI to cut and end-label DNA fragments before their separation in two dimensions provides a quantitative assessment of methylation at NotI sites that characteristically occur in CpG islands. We have undertaken quantitative analysis of two-dimensional DNA patterns to determine the extent of methylation heterogeneity at NotI sites between peripheral blood single-cell-derived T cell clones from the same individual. A total of 1,068 NotI-tagged fragments were analyzed. A subset of 156 fragments exhibited marked methylation heterogeneity at NotI sites between clones. Their average intensity among clones correlated with their intensity in uncultured, whole-blood-derived T cells, indicating that the methylation heterogeneity observed in clones was largely attributable to methylation heterogeneity between the individual cells from which the clones were derived. We have cloned one fragment that exhibited variable NotI-site methylation between clones. This fragment contained a novel CpG island for a gene that we mapped to chromosome 4. The methylation status of the NotI site of this fragment correlated with expression of the corresponding gene. Our data suggest extensive diversity in vivo in the methylation and expression profiles of individual T cells at multiple unrelated loci across the genome.

Base Composition↗
PubMed1999

Role of DNA methylation in the regulation of cell function.

The methylation of DNA helps stabilize chromatin in an inactive configuration and inhibits gene transcription. This mechanism of gene regulation is involved in essential genetic events including differentiation, genomic imprinting, and X chromosome inactivation. The alteration of methylation patterns can result in abnormal gene expression, with significant pathologic effects including carcinogenesis, autoimmunity, and some of the changes in gene expression associated with aging. The mechanisms establishing, maintaining, and modifying methylation patterns in normal and pathologic states are only now becoming understood, as are the mechanisms relating DNA methylation to gene expression and chromosome inactivation. Further characterization of these mechanisms holds promise for delaying or preventing the changes in methylation patterns that contribute to cancer, autoimmunity, and aging.

Animals↗
PubMed1998

Haemophilus influenzae type b infections in Hong Kong.

A 5-year territory-wide retrospective survey of invasive Haemophilus influenzae type b (Hib) diseases in Hong Kong established that the annual incidence for children <5 years old was 2.7 per 100000 [95% confidence interval (CI), 2.0 to 3.5]. However, the corresponding annual incidence in Vietnamese refugees in Hong Kong was 42.7 per 100000 (95% CI 17.2 to 87.9), giving a relative risk of 18.5 (95% CI 8.3 to 41.0). The nasopharyngeal carriage rate of Hib was zero in 621 healthy Chinese children and 1.3% (95% CI 0.04 to 2.63%) in 300 healthy Vietnamese refugees 2 months to 5 years old in Hong Kong. The corresponding carriage rate of nontypable H. influenzae was 5.8% (95% CI 1.4 to 7.6%) in Chinese and 65.4% (95% CI 58.9 to 69.8) in Vietnamese. In a larger study of 1812 healthy Chinese children between 6 months and 5 years of age investigated by throat swabs, again no Hib was isolated but 141 children (7.8%) were found to be carriers of nontype b H. influenzae. In a study of 596 healthy Chinese children and adults, 25% had the protective level of anti-Hib antibody of >0.15 microg/ml by 1 year and 90% had reached >0.15 microg/ml by 6 years of age. There was some evidence that these "natural" antibodies against Hib in Hong Kong Chinese were cross-reacting antibodies against antigens on other encapsulated bacteria.

Antibodies, Bacterial↗
PubMed1997

Mechanisms of drug-induced lupus. III. Sex-specific differences in T cell homing may explain increased disease severity in female mice.

OBJECTIVE: To determine if sex-specific differences in lymphocyte trafficking could contribute to increased disease severity in female mice. METHODS: A lupus-like disease was induced by injecting male and female mice with procainamide-treated T cell clones. Trafficking was examined by labeling the injected cells with 51Cr or 5-chloromethylfluorescein diacetate. RESULTS: Females developed more autoimmune liver disease and greater titers of anti-DNA antibodies than did males, and 2-7 times more cells accumulated in the female spleens. Splenectomy prevented the development of autoantibodies and renal and liver disease. Oophorectomy decreased the splenic homing, autoantibody titer, and liver disease severity, to levels found in males. CONCLUSION: T cells traffic differently to the spleen in male and female mice, and the spleen appears to be essential in the disease process. This suggests that differences in T cell homing could contribute to sex-specific disease severity in this murine model, and also possibly in human disease.

Adoptive Transfer↗
PubMed1997

Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo.

OBJECTIVE: T cells treated with DNA methylation inhibitors overexpress lymphocyte function-associated antigen 1 (LFA-1), which results in autoreactivity, and the autoreactive cells cause a lupus-like disease in vivo, suggesting a mechanism by which some agents may cause drug-induced lupus. This study compared the effects of procainamide (Pca) and hydralazine (Hyd) with those of structural analogs, to determine if the degree of LFA-1 overexpression and T cell autoreactivity correlated with the ability of the agents to induce autoimmunity. METHODS: Cloned murine T helper 2 cells were treated with Pca, N-acetylprocainamide, Hyd, Phthalazine, or hydroxyurea (HU). The treated cells were then compared for LFA-1 overexpression, autoreactivity, and the ability to induce autoimmunity in vivo. RESULTS: Pca and Hyd were more potent than their analogs or HU in all 3 assays. CONCLUSION: The results support a relationship between LFA-1 overexpression, T cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and Hyd, but not the analogs, may cause drug-induced lupus.

Animals↗
PubMed1996

Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice.

Current theories propose that systemic lupus erythematosus develops when genetically predisposed individuals are exposed to certain environmental agents, although how these agents trigger lupus is uncertain. Some of these agents, such as procainamide, hydralazine, and UV-light inhibit T cell DNA methylation, increase lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) expression, and induce autoreactivity in vitro, and adoptive transfer of T cells that are made autoreactive by this mechanism causes a lupuslike disease. The mechanism by which these cells cause autoimmunity is unknown. In this report, we present evidence that LFA-1 overexpression is sufficient to induce autoimmunity. LFA-1 overexpression was induced on cloned murine Th2 cells by transfection, resulting in autoreactivity. Adoptive transfer of the transfected, autoreactive cells into syngeneic recipients caused a lupuslike disease with anti-DNA antibodies, an immune complex glomerulonephritis and pulmonary alveolitis, similar to that caused by cells treated with procainamide. These results indicate that agents or events which modify T cell DNA methylation may induce autoimmunity by causing T cell LFA-1 overexpression. Since T cells from patients with active lupus have hypomethylated DNA and overexpressed LFA-1, this mechanism could be important in the development of human autoimmunity.

Animals↗
PubMed1995

Invasive Haemophilus influenzae type b infections in children hospitalized in Hong Kong, 1986-1990. Hong Kong Hib Study Group.

A 5-year territory-wide retrospective survey of invasive Haemophilus influenzae type b diseases was conducted in Hong Kong. Between 1986 and 1990, 57 cases (28 male) were recorded in children less than 12 years old (37 cases of meningitis, 9 of septicaemia and 11 of bacteraemic pneumonia). The annual incidence for children less than 5 years old was 2.7 per 10(5) (95% confidence interval (CI) 2.0-3.5). Of the 57 cases, 39 were Chinese and 18 non-Chinese (7 Vietnamese refugees, 6 Caucasians, 5 others). The annual incidence in Vietnamese refugees less than 5 years old was 42.7 per 10(5) (95% CI 17.2-87.9), giving a relative risk of 18.5 (95% CI 8.3-41.0). Chinese patients (68%) were under-represented as Chinese accounted for at least 94% of the population. Moreover, 14 of the 39 Chinese patients had pre-existing medical problems, compared with only 1 of the 18 non-Chinese patients patients had pre-existing medical problems, compared with only 1 of the 18 non-Chinese patients (p = 0.022).

Child↗
PubMed1994

Current practices for monitoring ocular toxicity related to hydroxychloroquine (Plaquenil) therapy.

OBJECTIVE: Growing interest in aggressive early management of rheumatoid arthritis (RA) with hydroxychloroquine (alone or in combination with other immunomodulating drugs) is reason to review current practices for monitoring ocular toxicity in patients who take antimalarial therapy. METHODS: We surveyed by mail all ophthalmologists and rheumatologists in the State of Indiana about their practices in this regard. RESULTS: Twenty-nine of 31 rheumatologists (94%) responded. All but one recommended ophthalmologic examinations every 6 months and 41% would leave the choice of testing procedures to the ophthalmologist. Fifty percent had discontinued hydroxychloroquine because of a patient's failure to make and/or keep an appointment with the ophthalmologist. Of 213 ophthalmologists surveyed, 150 (70%) responded. Seventy-nine percent recommended semiannual examinations. Funduscopy, visual acuity, and color vision tests were reported to be performed routinely. Eleven of 13 retina specialists (85%), but only 25% of 127 general ophthalmologists, would obtain macular photographs (p < 0.001). Forty-two percent of general ophthalmologists, compared with 8% of retina specialists, would perform computerized perimetry (p < 0.001). Recognition of retinal hyperpigmentation as a classic sign was surprisingly low in both groups. Concurrent review of the medical records of 24 patients with RA or systemic lupus erythematosus showed extremely variable followup intervals for ophthalmologic examination; 7 of the 24 patients had no record of an ophthalmologic evaluation. CONCLUSION: As interest in the early, aggressive management of RA continues to grow, significant education needs to be devoted to the monitoring and diagnosis of ocular toxicity of hydroxychloroquine by both rheumatologists and ophthalmologists.

Adult↗
PubMed1992

Experimental comparison of laser and cryosurgical cilia destruction.

We compared cryosurgery with the argon and carbon dioxide lasers in a rabbit model to evaluate the permanence of eyelash destruction as well as the gross and histologic effects on the eyelid. Each modality was equally effective in preventing eyelash regrowth. Cryosurgery and the carbon dioxide laser produced the greatest acute soft tissue swelling; the carbon dioxide laser produced the most pronounced gross eyelid alterations. The argon laser produced minimal eyelid tissue change. Long-term histologic tissue alterations were not striking and were confined to eyelids treated with cryosurgery and the carbon dioxide laser. We conclude that, of the two lasers, the argon is the best suited to the clinical treatment of trichiasis: it is widely available, more precise in limiting contiguous tissue destruction when delivered through a slit lamp, and is safer for use near the eye.

Animals↗
PubMed1992

Spontaneous iris stromal cyst: a case report and review of literature.

Spontaneous iris stromal cysts are rare and usually are identified early in life. They resemble implantation iris cysts after nonsurgical and surgical trauma; both have an epithelium which usually is conjunctival in nature. However, in spontaneous iris stromal cysts, no ocular trauma history is found. We present a case report and review of literature.

Cysts↗