Search PubMed⌕ Search

Biomedical subjects

K H Chan

Publications and source records attributed to K H Chan.

At least 55 records · Page 3Linked to original sources

Re-emergence of fatal human influenza A subtype H5N1 disease.

Human disease associated with influenza A subtype H5N1 re-emerged in January, 2003, for the first time since an outbreak in Hong Kong in 1997. Patients with H5N1 disease had unusually high serum concentrations of chemokines (eg, interferon induced protein-10 [IP-10] and monokine induced by interferon gamma [MIG]). Taken together with a previous report that H5N1 influenza viruses induce large amounts of proinflammatory cytokines from macrophage cultures in vitro, our findings suggest that cytokine dysfunction contributes to the pathogenesis of H5N1 disease. Development of vaccines against influenza A (H5N1) virus should be made a priority.

Animals↗

Viral replication in the nasopharynx is associated with diarrhea in patients with severe acute respiratory syndrome.

The role of severe acute respiratory syndrome (SARS) coronavirus as an enteric pathogen was investigated in a cohort of 142 patients with SARS who were treated with a standard treatment protocol. Data from daily hematological, biochemical, radiological, and microbiological investigations were prospectively collected, and the correlation of these findings with diarrhea was retrospectively analyzed. Sixty-nine patients (48.6%) developed diarrhea at a mean (+/- standard deviation [SD]) of 7.6+/-2.6 days after the onset of symptoms. The diarrhea was most severe at a mean (+/-SD) of 8.8+/-2.4 days after onset, with a maximum frequency of 24 episodes per day (median, 5 episodes; range, 3-24 episodes). A higher mean virus load in nasopharyngeal specimens obtained on day 10 after the onset of symptoms was significantly associated with the occurrence of diarrhea (3.1 log10 vs. 1.8 log10 copies/mL; P=.01) and mortality (6.2 vs. 1.7 log10 copies/mL; P<.01). However, diarrhea was not associated with mortality. The lung and the gastrointestinal tract may react differently to SARS coronavirus infection. Additional investigation of the role of SARS coronavirus in the pathogenesis of diarrhea in patients with SARS should be conducted.

Adult↗

Molecular epidemiology of the novel coronavirus that causes severe acute respiratory syndrome.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly emerged disease caused by a novel coronavirus (SARS-CoV), which spread globally in early 2003, affecting over 30 countries. We have used molecular epidemiology to define the patterns of spread of the virus in Hong Kong and beyond. METHODS: The case definition of SARS was based on that recommended by WHO. We genetically sequenced the gene for the S1 unit of the viral spike protein of viruses from patients with SARS in Hong Kong (138) and Guangdong (three) in February to April, 2003. We undertook phylogenetic comparisons with 27 other sequences available from public databases (Genbank). FINDINGS: Most of the Hong Kong viruses (139/142), including those from a large outbreak in an apartment block, clustered closely together with the isolate from a single index case (HKU-33) who came from Guangdong to Hong Kong in late February. Three other isolates were genetically distinct from HKU-33 in Hong Kong during February, but none of these contributed substantially to the subsequent local outbreak. Viruses identified in Guangdong and Beijing were genetically more diverse. INTERPRETATION: The molecular epidemiological evidence suggests that most SARS-CoV from the outbreak in Hong Kong, as well as the viruses from Canada, Vietnam, and Singapore, are genetically closely linked. Three viruses found in Hong Kong in February were phylogenetically distinct from the major cluster, which suggests that several introductions of the virus had occurred, but that only one was associated with the subsequent outbreak in Hong Kong, which in turn spread globally.

Canada↗

Modeling the ozonation of herbicide 2,4-D through a kinetic approach.

A quantitative estimation of the ozonation of a herbicide 2,4-D solution through a kinetic approach was studied and modelled. The ozonation of 2,4-D was found to follow a pseudo-first-order kinetic and the degradation rates depended on the initial pH and on the ozone concentration. A model was proposed to quantitatively predict the pseudo-first-order rate constants of the decay of 2,4-D under different ozone concentrations and initial pH levels based on some useful and practical assumptions. The proposed model was able to successfully describe the reaction with insignificant errors; therefore another practical equation was proposed to size the contact tower for 2,4-D ozonation by ozone concentration (overdosed) and initial pH level.

2,4-Dichlorophenoxyacetic Acid↗

The system design of UV-assisted catalytic oxidation process--degradation of 2,4-D.

Unlike the conventional first- or second-order model, a novel approach to design for the removal of 2,4-dichlorophenoxy (2,4-D) by the UV-catalytic oxidation process (UVCOP) was investigated. Two distinctive parameters, initial decay rate and maximum oxidative capacity, were characterized. By using these parameters, the performance of the degradation of 2,4-D by UVCOP regarding to the reagent dosages could be successfully predicted. Low concentrations of ferrous ion was found to be a rate-limiting factor for the process while the dosage of hydrogen peroxide was concluded as a dominant species in determining the maximum oxidation capacities. This information can be used to optimize the treatment process and achieve the expected performance target; an "optimal-dose model" was developed accordingly. The model is an intelligent and useful tool to evaluate the optimal doses of hydrogen peroxide with the minimum dose of ferrous ion, which leads to a better design of the treatment process.

2,4-Dichlorophenoxyacetic Acid↗

An unconventional approach to studying the reaction kinetics of the Fenton's oxidation of 2,4-dichlorophenoxyacetic acid.

The Fenton's oxidation kinetics of herbicide 2,4-D at various [Fe(II)] and [H(2)O(2)] combinations was investigated and modelled through an unconventional approach. The reaction kinetics of 2,4-D degradation demonstrated a two-stage pattern of decay, where a very fast reactive stage was followed by a retardation stage due to the depletion of oxidants and to the competitive side-reactions of the intermediates (including 2,4-dichlorophenol, chlorohydroquinone and 2,6-dichlororesorcinol). A model characterized by two newly established constants, the initial decay rate and the maximum oxidative capacity, was proposed and proven capable of describing the two-stage process, which cannot easily be described by conventional first- or second-order kinetics approaches.

2,4-Dichlorophenoxyacetic Acid↗

In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds.

Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16 h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics.

Adult↗

Direct detection of rifampin-resistant mycobacterium tuberculosis in respiratory specimens by PCR-DNA sequencing.

This study evaluated the feasibility of a molecular strategy based on identification of Mycobacterium tuberculosis by IS6110 PCR or Cobas Amplicor PCR, and rpoB PCR-DNA sequencing of the 81-bp rifampin resistance determining region (RRDR) for direct detection of rifampin resistance in respiratory specimens. A collection of 2,138 respiratory specimens and 352 nonduplicate M. tuberculosis isolates (including 233 isolates from the evaluated respiratory specimens and an additional collection of 119 stored isolates) from Southern China was investigated. Using culture as the reference test, the overall diagnostic sensitivities of an acid-fast bacillus (AFB) smear, Cobas Amplicor PCR, IS6110 PCR were 54.5% (156 of 286), 86.7% (248 of 286), and 89.2% (255 of 286), respectively. The sensitivities of the rpoB PCR for the specimens with positive AFB smears and with positive PCR results in the IS6110 PCR and/or Cobas Amplicor PCR were 100% (156 of 156) and 92.3% (239 of 259), respectively. Of the 352 nonduplicate M. tuberculosis isolates, the agar proportion method for rifampin reported 39 resistant strains. Full agreement (352 of 352) was found with the agar proportion method and the genotype inferred from the rpoB DNA sequencing data for rifampin. Thirty-nine mutations of nine distinct kinds, eight point mutations, and one deletion within the RRDR were found in the 39 resistant strains. For the direct DNA sequencing performed on rpoB PCR-positive respiratory specimens, the concordance with the agar proportion method and the subsequent PCR-sequencing for the culture isolate was 100%. This strategy has potential application for direct and rapid diagnosis of rifampin-resistant M. tuberculosis in IS6110 PCR or Cobas Amplicor PCR-positive respiratory specimens.

Antibiotics, Antitubercular↗

Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings.

BACKGROUND: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. METHODS: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. RESULTS: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 micro g/ml and 50 micro g/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls-both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)-but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. CONCLUSIONS: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.

Adult↗

Viral loads in clinical specimens and SARS manifestations.

A retrospective viral load study was performed on clinical specimens from 154 patients with laboratory-confirmed severe acute respiratory syndrome (SARS); the specimens were prospectively collected during patients' illness. Viral load in nasopharyngeal aspirates (n = 142) from day 10 to day 15 after onset of symptoms was associated with oxygen desaturation, mechanical ventilation, diarrhea, hepatic dysfunction, and death. Serum viral load (n = 53) was associated with oxygen desaturation, mechanical ventilation, and death. Stool viral load (n = 94) was associated with diarrhea, and urine viral load (n = 111) was associated with abnormal urinalysis results. Viral replications at different sites are important in the pathogenesis of clinical and laboratory abnormalities of SARS.

Adult↗

Laboratory diagnosis of four recent sporadic cases of community-acquired SARS, Guangdong Province, China.

Four cases of severe acute respiratory syndrome (SARS) that occurred from December 16, 2003, to January 8, 2004, in the city of Guangzhou, Guangdong Province, China, were investigated. Clinical specimens collected from these patients were tested by provincial and national laboratories in China as well as members of the World Health Organization SARS Reference and Verification Laboratory Network in a collaborative effort to identify and confirm SARS-associated coronavirus (SARS-CoV) infection. Although SARS-CoV was not isolated from any patient, specimens from three patients were positive for viral RNA by reverse transcription-polymerase chain reaction assay, and all patients had detectable rises in SARS-CoV-specific antibodies. This study shows the effectiveness of a collaborative, multilaboratory response to diagnose SARS.

Adult↗

Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003.

BACKGROUND: An epidemic of severe acute respiratory syndrome (SARS) has been associated with an outbreak of atypical pneumonia originating in Guangdong Province, People's Republic of China. We aimed to identify the causative agent in the Guangdong outbreak and describe the emergence and spread of the disease within the province. METHODS: We analysed epidemiological information and collected serum and nasopharyngeal aspirates from patients with SARS in Guangdong in mid-February, 2003. We did virus isolation, serological tests, and molecular assays to identify the causative agent. FINDINGS: SARS had been circulating in other cities of Guangdong Province for about 2 months before causing a major outbreak in Guangzhou, the province's capital. A novel coronavirus, SARS coronavirus (CoV), was isolated from specimens from three patients with SARS. Viral antigens were also directly detected in nasopharyngeal aspirates from these patients. 48 of 55 (87%) patients had antibodies to SARS CoV in their convalescent sera. Genetic analysis showed that the SARS CoV isolates from Guangzhou shared the same origin with those in other countries, and had a phylogenetic pathway that matched the spread of SARS to the other parts of the world. INTERPRETATION: SARS CoV is the infectious agent responsible for the epidemic outbreak of SARS in Guangdong. The virus isolated from patients in Guangdong is the prototype of the SARS CoV in other regions and countries.

China↗

Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study.

BACKGROUND: We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS). METHODS: We followed up 75 patients for 3 weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods. FINDINGS: Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days. INTERPRETATION: The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage.

Administration, Oral↗

The mechanism of the surfactant-aided soil washing system for hydrophobic and partial hydrophobic organics.

A surfactant-aided soil washing mechanism is proposed in this study by examining nine common organic contaminants, which were divided into two groups, hydrophobic compounds and partial hydrophobic compounds, depending on the respective soil partitioning of contaminants, K(oc). The presence of a free non-aqueous phase liquid in the soil washing system is critical to determine the soil washing performance curves. A mathematical model is proposed to describe soil-washing performance at various surfactant concentrations. The resulting slopes and intercepts from the model for the performance prediction are linearly related to K(oc). In addition, a transition zone between the hydrophobic and partial hydrophobic compounds was observed, and has been used in verifying the proposed mechanism successfully by overdosing and underdosing the contaminants in the system.

Journal Article↗

Coronavirus as a possible cause of severe acute respiratory syndrome.

BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. METHODS: We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. FINDINGS: Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. INTERPRETATION: A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

Adult↗

The system design of atrazine oxidation by catalytic oxidation process through a kinetic approach.

A design method for the removal of atrazine (ATZ) by catalytic oxidation process (COP) was developed though examination of the reaction kinetics in various conditions. The reaction kinetics of ATZ decay in COP are found to consist of a reaction and a stagnant stage, while two characteristic constants, the initial decay rate and the oxidative capacity of the COP, are successfully derived and used to describe the two stages, respectively. The proposed model and the way to solve the two characteristic constants (the initial decay rate and the oxidative capacity) are capable of describing the ATZ degradation precisely in COP at different Fe(II) concentrations and [Fe(II)]/[H(2)O(2)] ratios, where the marginal [Fe(II)]/[ATZ] ratio at 10 is found to be the critical point to achieve a cost-effective treatment of ATZ by COP. A series of equations for practical completely mixed batch reactor design is also developed based on the two characteristic constants.

Atrazine↗