Chulaluk Komoltri

Vascular Leakage in Severe Dengue Virus Infections: A Potential Role for the Nonstructural Viral Protein NS1 and Complement

BACKGROUND Vascular leakage and shock are the major causes of death in patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Thirty years ago, complement activation was proposed to be a key underlying event, but the cause of complement activation has remained unknown. METHODS The major nonstructural dengue virus (DV) protein NS1 was tested for its capacity to activate human complement in its membrane-associated and soluble forms. Plasma samples from 163 patients with DV infection and from 19 patients with other febrile illnesses were prospectively analyzed for viral load and for levels of NS1 and complement-activation products. Blood and pleural fluids from 9 patients with DSS were also analyzed. RESULTS Soluble NS1 activated complement to completion, and activation was enhanced by polyclonal and monoclonal antibodies against NS1. Complement was also activated by cell-associated NS1 in the presence of specific antibodies. Plasma levels of NS1 and terminal SC5b-9 complexes correlated with disease severity. Large amounts of NS1, complement anaphylatoxin C5a, and the terminal complement complex SC5b-9 were present in pleural fluids from patients with DSS. CONCLUSIONS Complement activation mediated by NS1 leads to local and systemic generation of anaphylatoxins and SC5b-9, which may contribute to the pathogenesis of the vascular leakage that occurs in patients with DHF/DSS.

Predictor of core hypothermia and the surgical intensive care unit.

Inadvertent postoperative core hypothermia is associated with multiple physiological effects, especially in patients admitted to the intensive care unit (ICU). Despite previous reports of the relationship between patient, surgical, and anesthetic factors and immediate postoperative core hypothermia, this information might need to be reconsidered in the light of progress in surgery, anesthetic, and warming techniques. We designed this prospective study of 194 postgeneral surgical patients to assess the incidence, predictive factors, and outcome of core hypothermia (tympanic membrane core temperature [Tc] <36.0°C) at the time of admission to the general ICU in a large tertiary university medical center from December 2000 to March 2001. The following variables were studied: age, sex, body weight, body surface area, preoperative body temperature, ASA physical status, history of diabetic neuropathy, emergency surgery, surgical subspecialty performing surgery, type of surgery, type of anesthesia (general, regional, or combined epidural and general), temperature monitoring, use of a forced air warming technique, amount of fluid and blood replacement, duration of anesthesia, duration of surgery, and the ambient operating room temperature. Other outcomes, i.e., length of ICU stay and mortality, were also assessed. The incidence of core hypothermia was 57.1%, 41.3%, and 28.3% according to the definition of Tc <36.0°C, <35.5°C, and <35.0°C, respectively. Multiple logistic regression showed the following risk factors for core hypothermia: high ASA physical status (odds ratio, 2.87; 95% confidence interval [CI], 0.82–10.03 for ASA II; odds ratio, 8.35; 95% CI, 1.67–41.88 for ASA >II), magnitude of surgical procedure (odds ratio, 6.60; 95% CI, 1.66–26.19 for medium surgery; odds ratio, 22.23; 95% CI, 5.41–91.36 for major surgery), use of combined epidural and general anesthesia (odds ratio, 3.39; 95% CI, 1.05–10.88), and duration of surgery >2 h (odds ratio, 4.50; 95% CI, 1.48–13.68). Not using temperature monitoring seems to be a risk factor as well (odds ratio, 3.00; 95% CI, 0.87–10.12). Significant protective factors against core hypothermia were heavier body weight (odds ratio, 0.94; 95% CI, 0.89–0.98), higher preoperative body temperature (odds ratio, 0.31; 95% CI, 0.15–0.65), and warmer ambient operating room temperature (odds ratio, 0.67; 95% CI, 0.51–0.88). In conclusion, the incidence of core hypothermia (Tc <36.0°C) at the time of admission to the general ICU is still frequent. To reduce the incidence, more efforts and concern should be taken to prevent core hypothermia, especially in the patient with high ASA physical status, undergoing more intensive and lengthy surgery, and using combined epidural and general anesthesia.

Elevated virus loads of Kaposi's sarcoma-associated human herpesvirus 8 predict Kaposi's sarcoma disease progression, but elevated levels of human immunodeficiency virus type 1 do not

Kaposis sarcoma-associated herpesvirus (KSHV) is found in Kaposis sarcoma (KS), multicentric Castlemans disease, and primary effusion lymphomas. To prospectively evaluate KSHV load as a biomarker for KS clinical status and prognosis in a cohort of men with AIDS-related KS, 2 quantitative polymerase chain reaction (PCR) assays were developed and tested to determine KSHV peripheral blood mononuclear cell (PBMC) virus loads. Most patients (13/15) with good-prognosis KS had < or =1.5 log KSHV copies/10(5) PBMC by both quantitative competitive (QC) and real-time Applied Biosystems (ABI) PCR. Both assays provided 94% specificity for identifying the 16 patients without KS progression during 20 months of follow-up. QC-PCR and ABI-PCR exhibited 100% and 80% levels of diagnostic sensitivity, respectively, for identifying the 5 patients whose KS progressed. Neither dichotomized human immunodeficiency virus loads nor dichotomized CD4 counts predicted either KS progression or KS clinical stage (all positive predictive values < 30%). These results are evidence that the quantity of circulating KSHV in KS patients is biologically meaningful and is measurable with sufficient accuracy to provide clinically useful information.

The Canadian Neurological Scale and the NIHSS: Development and Validation of a Simple Conversion Model

Background: The Canadian Neurological Scale (CNS) and the National Institutes of Health Stroke Scale (NIHSS) are among the most reliable stroke severity assessment scales. The CNS requires less extensive neurological evaluation and is quicker and simpler to administer. Objective: Our aim was to develop and validate a simple conversion model from the CNS to the NIHSS. Methods: A conversion model was developed using data from a consecutive series of acute-stroke patients who were scored using both scales. The model was then validated in an external dataset in which all patients were prospectively assessed for stroke severity using both scales by different observers which consisted of neurology residents or stroke fellows. Results: In all, 168 patients were included in the model development, with a median age of 73 years (20–94). Men constituted 51.8%. The median NIHSS score was 6 (0–31). The median CNS score was 8.5 (1.5–11.5). The relationship between CNS and NIHSS could be expressed as the formula: NIHSS = 23 – 2 × CNS. A cohort of 350 acute-stroke patients with similar characteristics was used for model validation. There was a highly significant positive correlation between the observed and predicted NIHSS score (r = 0.87, p < 0.001). The predicted NIHSS score was on average 0.61 higher than the observed NIHSS score (95% CI = 0.31–0.91). Conclusions: The CNS can be reliably converted to the NIHSS using a simple conversion formula: NIHSS = 23 – 2 × CNS. This finding may have a practical impact by permitting reliable comparisons with NIHSS-based evaluations and simplifying the routine assessment of acute-stroke patients in more diverse settings.

Erythrocyte binding preference of avian influenza H5N1 viruses.

ABSTRACT Five erythrocyte species (horse, goose, chicken, guinea pig, and human) were used to agglutinate avian influenza H5N1 viruses by hemagglutination assay and to detect specific antibody by hemagglutination inhibition test. We found that goose erythrocytes confer a greater advantage over other erythrocyte species in both assays.

An economic evaluation of bupivacaine plus fentanyl versus ropivacaine alone for patient-controlled epidural analgesia after total-knee replacement procedure: a double-blinded randomized study.

Background and Objectives Total-knee replacement (TKR) surgery is one of the most painful orthopedic procedures after surgery. Opioid has been commonly combined with a local anesthetic to improve the quality of pain relief, but the treatment has opioid-related side effects. This study compared the cost effectiveness of patient-controlled epidural analgesia (PCEA) with 0.0625% bupivacaine plus fentanyl (BF) 3 μg/mL versus 0.15% ropivacaine alone (R) during the first 48 hours after TKR procedure. Methods This prospective randomized double-blined study was performed on 70 patients who underwent unilateral TKR procedure and received either BF or R after surgery. Visual analog scale (VAS) pain score at rest and upon movement, side effects, and cost of treatment were compared. Results Overall pain at rest and upon movement between groups was not significantly different (P = 0.58, 95% CI = 4.4 to −7.8 and P = 0.8, 95% CI = 6.4 to −8.2, respectively). Patients in the BF group experienced more pruritus and had more vomiting episodes than those in the R group (P = .015), whereas no difference occurred in other side effects. Nevertheless, patient satisfaction with pain management was higher in the BF group compared with that in the R group. In addition, pain treatment with bupivacaine and fentanyl was 18% less costly compared with ropivacaine alone. Conclusions Considering the economic evaluation, we conclude that PCEA with 0.0625% bupivacaine plus fentanyl 3 μg/mL is more cost effective and provides more patient satisfaction than PCEA with ropivacaine alone. However, use of epidural ropivacaine alone causes fewer opioid-related side effects, particularly pruritus and vomiting.

Epidemiology of sleep-related complaints associated with sleep-disordered breathing in Bangkok, Thailand

BACKGROUND This study assesses the prevalence of and risk factors for sleep-related complaints in Bangkok, Thailand. METHODS A representative sample of the Bangkok population was selected based on results of the 2000 Census. A total of 4680 participants underwent face-to-face interview with a 49-question sleep inventory. RESULTS Four percent of the total sampled (5.3% of men and 3.5% of women) complained of habitual snoring (>3 nights/week) and excessive daytime sleepiness (>3 days/week) for at least 3 months. These subjects were significantly (p<0.0001) older (41.4 vs. 36.7 years), had greater BMI (26.0 vs. 22.8 kg/m(2)), neck size (34.7 vs. 32.5 cms), and waist circumference (88.0 vs. 78.7 cms). They reported significantly shorter nocturnal sleep time, greater frequency of sleep disturbances and awakenings, unrefreshing sleep, choking during sleep, night sweats, nocturia, and bruxism. There was also a greater prevalence of cardiovascular and endocrine diseases. Multivariate analysis showed that male gender; BMI; waist size; and reports of witnessed apneas, unrefreshing sleep and night sweats were significant predictors of snoring and daytime sleepiness. CONCLUSION This is the first epidemiologic study investigating sleep-related complaints and associated health morbidities in the Thai population.

Prevalence and cumulative incidence of abnormal cervical cytology among HIV-infected Thai women: a 5.5-year retrospective cohort study

BackgroundCervical cancer is one of the most common AIDS-related malignancies in Thailand. To prevent cervical cancer, The US Public Health Service and The Infectious Disease Society of America have recommended that all HIV-infected women should obtain 2 Pap smears 6 months apart after the initial HIV diagnosis and, if results of both are normal, should undergo annual cytological screening. However, there has been no evidence in supporting whether this guideline is appropriate in all settings - especially in areas where HIV-infected women are living in resource-constrained condition.MethodsTo determine the appropriate interval of Pap smear screenings for HIV-infected Thai women and risk factors for subsequent abnormal cervical cytology, we assessed the prevalence, cumulative incidence and associated factors of cervical cell abnormalities (atypical squamous cell of undetermined significance or higher grades, ASCUS+) among this group of patients.ResultsThe prevalence of ASCUS+ was 15.4% at the first visit, and the cumulative incidence of ASCUS+ gradually increased to 37% in the first 3.5 years of follow-up appointments (first 7 times), and tended to plateau in the last 2 years. For multivariate correlation analysis, women with a CD4 count <350 cells/μL had a significant correlation with ASCUS+ (P = 0.043). There were no associations of subsequent ASCUS+ with age, pregnancy, contraceptive method, highly active anti-retroviral treatment, assumed duration of infection, or the CD4 count nadir level.ConclusionThere are high prevalence and cumulative incidence of ASCUS+ in HIV-infected Thai women. With a high lost-to-follow-up rate, an appropriate interval of Pap smear screening cannot be concluded from the present study. Nevertheless, the HIV-infected Thai women may require more than two normal semi-annual Pap smears before shifting to routinely annual cytologic screening.

Association of otoscopic findings and hearing level in pediatric patients with otitis media with effusion

OBJECTIVE To find the association between the abnormalities of tympanic membrane characteristics and the hearing level in pediatric patients with otitis media with effusion. METHODS Sixty-three pediatric patients with otitis media with effusion had undergone ear examinations by pneumatic otoscopy to assess the color, transparency, mobility, fluid level and retraction of the tympanic membrane. An audiogram was done in the same setting, average hearing threshold and air-bone gap were measured. Otoscopic findings and the result of the hearing test were analyzed to identify the association between the abnormalities of the tympanic membrane characteristics and elevated hearing threshold. RESULTS Hearing loss was found in 92.1% of the patients. Mean hearing level was 31.7+/-10.3 dB. From linear regression analysis, the patients with dull or opaque tympanic membrane had a significantly higher hearing threshold of 7.2 dB than the patient with translucent ear drum after adjusting for mobility and retraction. The patients with tympanic membrane retraction had a higher hearing threshold of 5.1 dB than the patient who had no retraction after adjusting for transparency and mobility. Mobility had a significant relationship to elevated hearing threshold in the univariate analysis but not in multivariable analysis. CONCLUSION Opacity and retraction were the two characteristics of abnormal tympanic membrane that were associated with elevated hearing threshold in the patients with otitis media with effusion. Hearing test is suggested if opacity or retraction of the tympanic membrane is found.

Clinicopathologic Features of Breast Carcinomas Classified by Biomarkers and Correlation with Microvessel Density and VEGF Expression: A Study from Thailand

BACKGROUND To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. MATERIALS AND METHODS One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER) +, HER2-, Ki-67≤14%], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. RESULTS Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. CONCLUSIONS The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.