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Paul K S Chan,
Nelson Lee,
Gavin M Joynt,
K W Choi,
Jo L K Cheung,
Apple C M Yeung, Philip Lam,
Rity Wong,
Bo-Wah Leung,
Hing-Yu So,
Wai-Yip Lam,
David C S Hui
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ABSTRACT: Aspartic acid to glycine substitution (D222G) of haemagglutinin subunit (HA1) was associated with adverse outcomes in 2009 pandemic influenza A (H1N1) infections.
To characterize the virological profile and antiviral response of patients infected with the HA1 D222G mutant.
Sixty-three adults admitted for pandemic influenza in Hong Kong were tested for D222G mutation by direct sequencing. Nasopharyngeal viral concentration on presentation was measured by real-time PCR to evaluate shedding from the upper respiratory tract. Serial upper and lower respiratory tract specimens were monitored to determine preferential tropism and document virological response to treatment.
The frequency of D222G infection was 17.4% among cases with severe pneumonia, and 26.7% among cases requiring intensive care. Altogether, four sporadic D222G cases spread across the first and second waves in Hong Kong were detected. A significant association between D222G infection with severe pneumonia (100% vs. 32.2%, P=0.015) and intensive care admission (100% vs. 18.6%, P=0.002) was observed. D222G was associated with lower concentrations of virus in the upper respiratory tract compared to wildtype, but persisted in the lower respiratory tract at high concentrations, despite clearance from the upper respiratory tract following antiviral treatment.
These observations suggest that D222G can arise de novo, sheds less virus from the upper respiratory tract and may be less transmissible, but more pneumotropic and more resistant to antiviral treatment. D222G is associated with a higher chance of developing critical disease. Lower respiratory tract specimen is needed for a reliable detection of this mutant.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 02/2011; 50(4):320-4. · 3.12 Impact Factor
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ABSTRACT: We evaluated the effectiveness of diode laser trans-scleral cyclophotocoagulation (TSCPC) on intraocular pressure (IOP) in nine patients having raised IOP following use of silicone oil (SO) for retinal detachment (RD) surgery in a retrospective observational case series. Diode laser TSCPC was applied at a power setting of 1.75 to 2.5 watts, for two sec with a maximum of 30 applications. The patients were followed up for 40 to 312 weeks. The mean pre-laser IOP was 32.06 mm Hg (SD 7.32). The mean post-laser IOP at one month, three months and six months was 17.89 mm Hg (SD 8.23), 21.89 mm Hg (SD 8.16) and 21.67 mm Hg (SD 7.55) respectively. The final IOP (at the last follow-up) was 19.56 mm Hg (SD 7.85) (P=0.021). Seven of them had undergone SO removal. In our observation, effectiveness of TSCPC in long-term control of SO-induced ocular hypertension was limited as compared to short-term control of IOP.
Indian Journal of Ophthalmology. 01/2011;
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Nelson Lee,
Paul K S Chan,
Chun Kwok Wong,
Ka-Tak Wong,
Kin-Wing Choi,
Gavin M Joynt, Philip Lam,
Martin C W Chan,
Bonnie C K Wong,
Grace C Y Lui,
Winnie W Y Sin,
Rity Y K Wong,
Wai-Yip Lam,
Apple C M Yeung,
Ting-Fan Leung,
Hing-Yu So,
Alex W Y Yu,
Joseph J Y Sung,
David S C Hui
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ABSTRACT: Little is known about the virological and inflammatory responses of severe pandemic 2009 influenza A(H1N1) virus pneumonia during antiviral treatment.
In a prospective observational study, we recruited consecutive adults hospitalized with confirmed pandemic 2009 H1N1 infection during a 16-week period. Nasopharyngeal aspirate and non-respiratory samples (blood, stool and urine) were collected at presentation, and serial nasopharyngeal flocked swabs (NPFS) and tracheal aspirates (TA) were collected after initiating oseltamivir treatment for quantitative viral RNA assay, using real-time reverse transcriptase-PCR. Serial plasma samples were collected for cytokine/chemokine assay using cytometric bead array. Patients with severe pneumonia (lung infiltrates and hypoxaemia) were compared to those with milder illnesses.
A total of 66 patients were studied (mean age 43 ±20 years); 28 (42%) developed severe pneumonia, of whom 10 (15%) required intubation. Severe pneumonia was associated with older age, dyspnoea, delayed presentation >2 days from onset, extrapulmonary virus detection (13-28%) and higher viral concentration despite late-presentation (multiple linear regression, β=0.94, 95% confidence interval 0.15-1.74; P=0.02). Patients with severe pneumonia exhibited slow viral clearance with oseltamivir treatment, particularly in the lower respiratory tract (median [interquartile range] durations of RNA positivity after antiviral initiation were NPFS 6.0 days [3.0-8.0], TA 11.0 days [7.8-14.3] versus milder illness group NPFS of 2.0 days [1.0-3.0] days; P<0.01). High viral load in lower respiratory tract despite upper-tract RNA negativity and viral rebound after stopping treatment were noted in some patients. H275Y mutation was absent. High plasma levels of interleukin (IL)-6, CXCL-8 (IL-8), CCL2 (monocyte chemoattractant protein-1) and soluble tumour necrosis factor receptor-1 were observed, which correlated with the extent and progression of pneumonia in hospital.
In severe 2009 H1N1 pneumonia, viral clearance is slow with treatment, particularly in the lower respiratory tract. A more sustained antiviral regime appears warranted.
Antiviral therapy 01/2011; 16(2):237-47. · 3.16 Impact Factor
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Cornea 09/2009; · 1.73 Impact Factor
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Charles D Gomersall,
Gavin M Joynt, Philip Lam,
Thomas Li,
Florence Yap,
Doris Lam,
Thomas A Buckley,
Joseph J Y Sung,
David S Hui,
Gregory E Antonio,
Anil T Ahuja,
Patricia Leung
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ABSTRACT: To document the outcome and determine prognostic factors for patients with severe acute respiratory syndrome who require admission to an intensive care unit.
Observational cohort study involving retrospective analysis of demographic, clinical, laboratory and radiological data.
Adult intensive care unit in a tertiary referral university hospital involved in a major outbreak of severe acute respiratory syndrome (SARS).
The first 54 patients admitted with SARS to an intensive care unit (ICU). All were treated with corticosteroids, ribavirin, broad spectrum antimicrobials and supportive therapy.
None.
All patients were admitted for respiratory failure. The median APACHE II score was 11 (interquartile range 8-13). At 28 days 34 patients (63%; 95% CI 49.6-74.6) were alive and not mechanically ventilated. Six patients were alive but ventilated (11.3%; 95% confidence interval 5.3-22.6) and 14 had died (25.9%; CI 16.1-38.9). Seven of 27 ventilated patients developed evidence of barotrauma (25.9%; 95% CI 13.2-44.7). Median maximal multiple-organ dysfunction score was 5 (interquartile range 3.3-9). Median maximal respiratory dysfunction score was 3 (interquartile range 3-4). Increased age, severity of illness, lymphocyte count, decreased steroid dose, positive fluid balance, chronic disease or immunosuppression and nosocomial sepsis were associated with poor outcome on univariate analysis. Poor outcome was defined as death or need for mechanical ventilation at 28 days after ICU admission.
Mortality amongst critically ill patients with SARS is high. It causes predominantly severe respiratory failure, with little other organ failure, and a high incidence of barotrauma amongst those requiring mechanical ventilation.
Intensive Care Medicine 04/2004; 30(3):381-7. · 5.40 Impact Factor
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ABSTRACT: To evaluate thin-section computed tomographic (CT) abnormalities in patients in the intensive care unit during the late stage of adult respiratory distress syndrome (ARDS) caused by severe acute respiratory syndrome (SARS).
Eight patients in the late stage of ARDS (ie, more than 2 weeks after onset) were imaged with thin-section CT. Images were evaluated for ground-glass opacification, consolidation, interstitial thickening, evidence of fibrosis, and any other abnormalities. Patient records were reviewed, and relevant respiratory and ventilatory parameters, total steroid dose, and outcome were recorded.
All patients received high-dose pulse methylprednisolone (minimum, 2.5 g total), and all patients who received ventilation received low-pressure, low-volume ventilation. Five patients received prolonged mechanical ventilation (for more than 14 days), one received ventilation for 72 hours, and two patients did not receive ventilation. Three patients died, four were discharged from the hospital, and one continued to require ventilation. Ground-glass opacification and interstitial thickening were present at CT in all eight patients. Consolidation was present in six patients. Three patients had evidence of fibrosis. Patients who received long-term ventilation, those who received short-term ventilation, and those who did not receive ventilation had similar pulmonary changes at CT. Pulmonary cysts, most of which were small (<1 cm), were present in five patients. Cysts were present in one patient who received only short-term low-pressure and low-volume ventilation and in one patient who received no mechanical ventilation.
The CT features of late-stage ARDS caused by SARS are similar to those seen in late-stage ARDS of other causes, with no apparent differences between patients who do and patients who do not receive prolonged mechanical ventilation. The presence of cysts in one patient who received short-term and one patient who received no mechanical ventilation suggests that severe SARS-induced ARDS may independently result in cyst formation.
Radiology 02/2004; 230(2):339-46. · 5.73 Impact Factor
