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Biomedical subjects

W S Chan

Publications and source records attributed to W S Chan.

At least 19 recordsLinked to original sources

Extremely low exposure of a community to severe acute respiratory syndrome coronavirus: false seropositivity due to use of bacterially derived antigens.

Estimates of seropositivity to a new infectious agent in a community are useful to public health. For severe acute respiratory syndrome (SARS), the figures are conflicting. Herein, we screened 12,000 people in a community stricken by SARS 10 months previously and found 53 individuals (0.44%) who had immunoglobulin G antibodies to the SARS coronavirus (SARS-CoV) nucleocapsid (N) produced in bacteria. However, only seven of these (group 1) had sera which also reacted with the native N antigen expressed in SARS-CoV-infected Vero cells, N-transfected 293T cells, and tissues of infected SARS patients. Of these, six individuals had had SARS previously. The remaining person, as well as the 46 other individuals (group 2), were healthy and had no history of SARS. Group 1 antibodies recognized epitopes located slightly differently in N from those of group 2 antibodies, and a mouse hybridoma antibody resembling the former type was generated. Unusually, group 2 antibodies appeared to recognize cross-reactive bacterial epitopes that presumably were posttranslationally modified in eukaryotes and hence were probably not induced by SARS-CoV or related coronaviruses but rather by bacteria. The N antigen is thus highly unique. The extremely low rate (0.008%) of asymptomatic SARS infection found attests to the high virulence of the SARS-CoV virus.

Animals↗

Methods for estimating the case fatality ratio for a novel, emerging infectious disease.

During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital.

Communicable Diseases, Emerging↗

Brisk walking, fitness, and cardiovascular risk: a randomized controlled trial in primary care.

STUDY OBJECTIVE: To examine the effects of 30 min of self-paced, non-supervised, brisk walking, 5 days per week on the health and fitness of people aged 50-65 years. DESIGN: Randomized controlled trial. Members of the intervention group (n = 21) were directed to walk briskly for 30 min, 5 days per week, for 12 weeks. Individuals were given the choice to complete the 30 min of walking in one session or in shorter bouts of no less than 10 min. They were asked to record in a diary the time spent walking and the number of steps taken during a single walk using a pedometer. Participants in the control group (n = 10) were asked to maintain their habitual lifestyle and not change their activity or dietary habits. Measurements of body mass index (BMI), waist/hip ratio (WHR), blood pressure, functional capacity, total cholesterol, triglyceride, and lipoprotein subfractions were taken before and after the program. Changes in 10-year risk estimate for coronary heart disease and stroke were calculated using Framingham risk equations. SETTING: Three urban general practices patients: 31 healthy, sedentary 50- to 65-year-old participants recruited following contact by their general practitioner. MAIN RESULTS: The mean time spent walking by the intervention group was 27.72 (+/-9.79) min/day: their adherence to the protocol was 90.3%. Significant decreases in systolic and diastolic blood pressure, reduction in stroke risk, and increased functional capacity were found within the walking group between baseline and 12-week measurements. No changes were found in these parameters within the control group. Significant reductions in 10-year risk of CHD were observed in both groups. No significant changes were found in lipid levels or anthropometric measurements in either group. CONCLUSIONS: The study provides evidence for the benefit to fitness and cardiovascular risk of the "30-min brisk walking, 5 days a week" message to people aged 50-65 years who participated in an unsupervised home-based walking program. Further study to overcome the problem of poor recruitment and determine the minimum effective dose of exercise to improve cardiovascular risk prediction scores is required.

Aged↗

Suspected pulmonary embolism in pregnancy: clinical presentation, results of lung scanning, and subsequent maternal and pediatric outcomes.

BACKGROUND: Ventilation-perfusion (VQ) scanning is used when pulmonary embolism (PE) is suspected during pregnancy; however, the distribution of lung scan results and safety of VQ scanning have never been studied. OBJECTIVE: To study the distribution of lung scan results and safety of VQ scanning as well as the safety of withholding anticoagulation therapy following a normal or nondiagnostic scan in pregnant women. METHODS: The study group comprised 120 consecutive pregnant women who presented with suspected PE. Clinical data were collected, and the lung scans were reinterpreted by 2 independent experts. Subsequent pregnancy and pediatric outcomes were determined by direct patient follow-up. RESULTS: During the study period, 120 pregnant women (mean age, 32 years) underwent 121 VQ scans. Eight cases (6.6%) were already receiving treatment for venous thromboembolism prior to VQ scanning. In the remaining 113 scans, 83 (73.5%) were interpreted as normal, 28 (24.8%) as nondiagnostic, and 2 (1.8%) as high probability. In the 104 women who did not receive anticoagulation therapy following lung scanning (80 normal and 24 nondiagnostic), no venous thromboembolic events were reported (mean [range] length of follow-up, 20.6 [0.5-108] months). Examination of pediatric data from 110 live births (90.2%) (mean [range] age, 20.5 [0.5-100] months) revealed no increase in the rates of congenital and developmental anomalies. CONCLUSIONS: The prevalence of high-probability VQ scans in pregnant women with suspected PE and probable PE is very low. Withholding anticoagulation in pregnant women with normal or nondiagnostic VQ scans is probably safe. In addition, pediatric risks from VQ scans are low. Large prospective studies are needed to evaluate diagnostic strategies for pregnant women with suspected PE.

Anticoagulants↗

Antithrombotic therapy during pregnancy.

Antithrombotic therapy is required during pregnancy for the prevention and treatment of venous and arterial thromboembolism and for the prevention of pregnancy loss in women at risk. The choice of anticoagulant for venous thromboembolism during pregnancy is limited to unfractionated heparin or low molecular weight heparin because the use of warfarin is relatively contraindicated. Much of the information surrounding the pharmacokinetics and dosing of unfractionated heparin and low molecular weight heparin obtained from non-pregnant patients has been applied to pregnant women. Whether this is appropriate in the presence of significant physiological changes in pregnancy is unclear. Specific to pregnancy and unfractionated heparin use, activated partial prothrombin time may be unreliable. In addition, the appropriate dosing of low molecular weight heparin is uncertain. Because venous thromboembolism can cause significant maternal morbidity and mortality, these important issues surrounding appropriate drug dosing of anticoagulants should be addressed.

Female↗

Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis.

Offspring of women with pregestational diabetes mellitus are at increased risk for congenital malformations, largely attributable to poor periconceptional glycaemic control. We assessed the effect of preconception care in reducing congenital malformations, in a meta-analysis of published studies of preconception care in women with diabetes mellitus. Articles were retrieved from Medline (1970 to June 2000) and Embase (1980 to June 2000), and data abstracted by two independent reviewers. The rates and relative risks (RR) for major and minor congenital malformations were pooled from all eligible studies using a random effects model, as were early first-trimester glycosylated haemoglobin values. In 14 cohort studies, major congenital malformations were assessed among 1192 offspring of mothers who had received preconception care, and 1459 offspring of women who had not. The pooled rate of major anomalies was lower among preconception care recipients (2.1%) than non-recipients (6.5%) (RR 0.36, 95%CI 0.22-0.59). In nine studies, the risk for major and minor anomalies was also lower among women who received preconception care (RR 0.32, 95%CI 0.17-0.59), as were the early first-trimester mean glycosylated haemoglobin values (pooled mean difference: 2.3%, 95%CI 2.1-2.4). Women who received preconception care were, on average, 1.8 years older than non-recipients, and fewer smoked (19.6% vs. 30.2%). Only one study described the routine use of periconception folic acid. Out-patient preconception care probably reduces the risk of major congenital anomalies among the offspring of women with pregestational diabetes mellitus. Because many women with diabetes neither plan their pregnancy nor achieve adequate glycaemic control before conception, strategies are needed to improve access to these programs, and to maximize those interventions associated with improved pregnancy outcome, such as smoking cessation and folic acid use.

Adult↗

Intubation through intubating laryngeal mask with and without a lightwand: a randomized comparison.

The combined use of a lightwand and the intubating laryngeal mask airway (ILMA) was compared with the use of the ILMA alone to determine whether the combination was a more efficient method of endotracheal intubation. One hundred healthy patients were randomly assigned to two groups. After induction of anaesthesia, Group A patients were intubated blindly through the ILMA while in Group B, intubation was guided by a lightwand. A sequence of standard manoeuvres was followed it attempts at intubation failed. The number of manoeuvres used, the time taken for successful intubation and complications associated with intubation were recorded. Intubations were successful in all patients, but the mean endotracheal intubation time was longer in Group A than in Group B (38.3 +/- 10.4 s versus 26.4 +/- 9.1 s, P < 0.001). The number of patients who needed one or more manoeuvres was significantly higher in Group A than in Group B (76% versus 42%, P = 0.001). We conclude that the lightwand is a useful adjunct in endotracheal intubation through an ILMA.

Adult↗

Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature.

BACKGROUND: The management of women with prosthetic heart valves during pregnancy poses a particular challenge as there are no available controlled clinical trials to provide guidelines for effective antithrombotic therapy. Oral anticoagulants such as warfarin sodium cause fetal embryopathy; subcutaneous administration of heparin sodium has been reported to be ineffective in preventing thromboembolic complications. OBJECTIVE: To identify the risks of maternal and fetal complications in women with mechanical heart valves treated with different anticoagulation regimens during pregnancy. METHODS: We performed a systematic review of the literature to determine pooled estimates of maternal and fetal risks associated with the 3 commonly used approaches: (1) oral anticoagulants (OA) throughout pregnancy, (2) replacing OA with heparin in the first trimester (from 6-12 weeks' gestation), and (3) heparin use throughout pregnancy. Fetal outcomes included spontaneous abortions and fetopathic effects, and maternal outcomes were major bleeding, thromboembolic complications, and death. RESULTS: The use of OA throughout pregnancy is associated with warfarin embryopathy in 6.4% (95% confidence interval [CI], 4.6%-8.9%) of livebirths. The substitution of heparin at or prior to 6 weeks, and continued until 12 weeks, eliminated this risk. Overall risks for fetal wastage (spontaneous abortion, stillbirths, and neonatal deaths) were similar in women treated with OA throughout, compared with women treated with heparin in the first trimester. Maternal mortality was 2.9% (95% CI, 1.9%-4.2%). Maj or bleeding events occurred in 2.5% (95% CI, 1.7%-3.5%) of all pregnancies, most at the time of delivery. The regimen associated with the lowest risk of valve thrombosis (3.9%; 95% CI, 2.9-5.9%) was the use of OA throughout; using heparin only between 6 and 12 weeks' gestation was associated with an increased risk of valve thrombosis (9.2%; 95% CI, 5.9%-13.9%). CONCLUSIONS: Thromboembolic prophylaxis of women with mechanical heart valves during pregnancy is best achieved with OA; however, this increases the risk of fetal embryopathy. Substituting OA with heparin between 6 and 12 weeks reduces the risk of fetopathic effects, but with an increased risk of thromboembolic complications. The use of low-dose heparin is definitely inadequate; the use of adjusted-dose heparin warrants aggressive monitoring and appropriate dose adjustment. Large prospective trials to determine the best regimen for these women are needed.

Administration, Oral↗

Photochemical decontamination of red blood cell concentrates with the silicon phthalocyanine PC 4 and red light.

Various approaches are being developed for virus inactivation of red blood cell concentrates (RBCC) in order to increase the safety of the blood supply. We have been studying the silicon phthalocyanine Pc 4 for this purpose, a photosensitizer activated with red light. Pc 4 targets the envelope of pathogenic viruses such as HIV. To protect RBC during the process two main approaches are used: (i) inclusion of quenchers of reactive oxygen species produced during the treatment. Tocopherol succinate was found to be most effective for this purpose; (ii) formulation of Pc 4, a lipophilic compound, in liposomes that reduce its binding to RBC but not to viruses. As a light source we used a light emitting diode array emitting at 670-680 nm. An efficient mixing device ensures homogenous light exposure during treatment of intact RBCC. Treatment of 50 ml RBCC with 5 microM Pc 4 and 18 J/cm(2) light results in the inactivation of > or = 5.5 log(10) HIV, > or = 6.3 log(10), VSV and > or = 5 log(10) of PRV and BVDV. The relative sensitivities of these viruses based on the slope of virus kill versus light dose are 1.0, 1.25, 1.5 and 1.9 for HIV, VSV, PRV and BVDV, respectively. To achieve the same level of virus inactivation in 350 ml RBCC, the light dose needed is 40 J/cm(2). HIV actively replicating in CEM cells is as sensitive as cell-free and HIV in latently infected cells is 3-4 times more sensitive. Parasites that can be transmitted by blood transfusion (P. falciparum and T. cruzi) are even more sensitive than viruses. Following treatment, RBCC can be stored for 28 days at 4 degrees C with haemolysis below 1%. Previous studies under less favourable conditions showed that baboon RBC circulated with an acceptable 24 hr recovery and half-life. Genetic toxicological studies of Pc 4 with or without light exposure (mutagenicity in bacteria, mammalian cells in vitro and clastogenicity in vivo) were negative. We conclude that a process using Pc 4 and red light can potentially reduce the risk of transmitting pathogens in RBCC.

Animals↗

Initial characterization of the complement activating compounds in extracts of smokeless tobacco.

Aqueous extracts of smokeless tobacco (ST) have been shown to be potent activators of complement. However, the mechanisms by which smokeless tobacco activates complement are not well understood. This study was undertaken to identify the complement activating compounds in ST extracts. The approximate molecular size of the activating agent(s) in smokeless tobacco was determined by dialyzing aqueous extracts of loose leaf chewing tobacco (1S1), dry snuff (1S2), and moist snuff (1S3). Following dialysis (total dilution effect of 1:10(9)), using a membrane with a molecular weight retention limit of 12-14 kDa, all extracts retained full capacity to activate serum complement as determined by a hemolytic assay. Fractionation of the extracts by gel filtration chromatography revealed that the complement activating agents in ST were high molecular weight compounds that eluted between 400 kDa and the void volume (1500 kDa) of a Sephacryl S300 column. The high molecular weight complement-activating peak was isolated and found to be a more potent complement activator than the unfractionated extract. The chemical nature of the complement activating compounds was determined by subjecting the extracts to boiling for 30 min, an organic extraction with chloroform/methanol 2:1, or treatment with a DNAse/RNAse enzyme cocktail. None of these treatments destroyed the capacity of ST extracts to activate complement, suggesting that the activating agents may be carbohydrate-like. Finally, an extraction protocol designed to remove polyphenols significantly diminished the complement activating capacity of the ST extracts. These results clearly demonstrate that the complement activating substances in smokeless tobacco extracts may be large (>400 kDa) polyphenol-containing compounds (i.e. tannins). Identification of this agent(s) will be important for distinguishing the mechanism of smokeless tobacco-induced complement activation.

Complement Activation↗

The use of orthographic analogies in learning to read Chinese.

Two studies, comprising training in phonological analogy and semantic analogy with pre-and post-training assessments, were conducted to investigate whether young children made orthographic analogies in learning to read a nonalphabetic script, Chinese, as alphabetic readers do. Twenty Chinese first-graders and 20 third-graders participated in each of the studies. The results showed that not only the third-graders, but also the first-graders made phonological analogies by the phonetic (i.e. the orthographic component in a Chinese character that provides sound cues) and semantic analogies by the radical (i.e. the orthographic component that provides meaning cues). It was, therefore, suggested that the roles and functions of the phonetics and radicals could be taught explicitly in school from an early age to help improve children's reading skills.

Analysis of Variance↗

Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the period of risk and the leg of presentation.

UNLABELLED: We performed a meta-analysis of all published studies of deep vein thrombosis during pregnancy and the puerperium using MEDLINE between 1966 and May 1998. Data were pooled using a random effects model. Fourteen studies included relevant information on deep vein thrombosis in pregnancy or the puerperium, and used objective testing to diagnose deep vein thrombosis. The pooled event rate for left sided or bilateral deep vein thrombosis was 82.2 percent (95 percent CI 75.1 to 87.5). There was no statistical evidence of heterogeneity for this figure (P = .08). Twelve studies reported on the trimester in which deep vein thrombosis was diagnosed. The deep vein thrombosis event rate during the first trimester was 21.9 percent (95 percent CI 17.4 to 27.3), 33.7 percent (95 percent CI 28.1 to 39.8) during the second trimester, and 47.6 percent (95 percent CI 39.2 to 56.2) for the third trimester. Heterogeneity testing was not significant. Nine studies compared deep vein thrombosis events between the antepartum and puerperium periods, with 65.5 percent (95 percent CI 58.1 to 72.1) arising during pregnancy, and 34.5 percent (95 percent CI 27.9 to 41.9) postpartum (P = .08, not heterogeneous). Using these figures, the estimated relative distribution of 100 deep vein thrombosis events during pregnancy and the puerperium would be 0.23 per day during pregnancy, and 0.82 per day in the postpartum period. During pregnancy and the puerperium, deep vein thrombosis is more likely to arise in the left leg. More than half of all deep vein thromboses during pregnancy occur during the first and second trimesters. Furthermore, during the puerperium, the risk of developing deep vein thrombosis is significantly higher than antepartum. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to understand the incidence and distribution of DVTs during pregnancy and to be able to appreciate the differing risk of DVT during the various time periods in a pregnancy.

Female↗

Low molecular weight heparin use during pregnancy: issues of safety and practicality.

UNLABELLED: Low molecular weight heparin is an important agent for the treatment and prophylaxis against venous thromboembolism during pregnancy. It offers several distinct advantages over unfractionated heparin. A systematic search was performed of the literature review of low molecular weight heparin use in pregnancy and presents a practical approach to its use by obstetricians and internists. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to understand the pharmacology and the elimination of low molecular weight heparin, the potential side effects and how to appropriately monitor the drug, and the indications and management of the low molecular weight heparins during pregnancy.

Blood Coagulation↗

What is the optimal management of pregnant women with valvular heart disease in pregnancy?

Women with mechanical heart valves require anticoagulation during pregnancy. Continued anticoagulation with coumadin throughout the first trimester can result in foetopathic effects in 6.4% (95% CI, 4. 6-8.9%) of cases. Replacement of warfarin with heparin between 6 and 12 weeks' gestation eliminates this risk. Although warfarin does cross the placenta, adverse central nervous system effects associated with its use are very few. Warfarin is effective in preventing maternal thromboembolic complications, while the effectiveness of heparin in preventing valve thrombosis is unproven. The optimal management (grade C2 recommendation) of women with mechanical heart valves may involve the use of warfarin throughout pregnancy except for two time periods - between 6 and 12 weeks' gestation and after 36 weeks of gestation. During these times, adjusted-dose unfractionated heparin should be used to rigorously maintain a therapeutic mid-interval activated partial thromboplastin time of 2.0 to 2.5 times the control. The additional use of low-dose aspirin should be considered, particularly in women with high-risk valves, women with previous transient ischaemic attacks and/or strokes, and women with atrial fibrillation.

Anticoagulants↗

Pregnancy in chronic dialysis: a review and analysis of the literature.

UNLABELLED: Pregnancy is uncommon in end-stage renal failure, particularly in patients requiring dialysis. We reviewed the literature from 1965 to date, seeking an optimal way of dialyzing pregnant women after encountering one such patient METHODS: We searched the English literature by cross-referencing "pregnancy" with "hemo-" or "peritoneal dialysis" and "renal failure". Eighty-six pregnancies worldwide were found to which we added one case of our own. Various independent factors were studied against gestational age at delivery using uni- and multivariate analysis. These factors included mother's age, previous delivery, diagnoses of renal disease, dialysis duration prior to pregnancy, gestational age at onset of dialysis, dialysis type, level of hemoglobin during pregnancy, BUN and creatinine targets, BUN/creatinine ratio, dialysis intensity at the beginning and end of pregnancy, influence of erythropoietin and dialysis complications. RESULTS: Of the 87 pregnancies, 12% resulted in stillbirths, 9% of neonates died prior to discharge. The mean gestational age at delivery was 32 +/- 5 weeks, and the mean birth weight 1604 +/- 652 g. Two congenital abnormalities and one twin pregnancy were reported. 48% of deliveries were premature. Pre-eclampsia was reported in 11%, and worsening hypertension in 17%. CAPD was used in 25 and hemodialysis in 62 patients. Fetal survival was similar in both cases (72% vs 82%), although incidence of various dialysis complications differed. The conventional dialysis goals of a low target BUN level and hemoglobin for pregnant patients were not factors in predicting fetal outcome. The number of hemodialyses/week were negatively correlated (R = -0.35, P = 0.061), but the hours of dialysis positively correlated (R = 0.42, p = 0.035) to gestational age. Fetal survival was independently influenced by creatinine level [564 micromol/L when baby survived vs 788 micromol/L when baby died (p = 0.021)], BUN/creatinine ratio (50 vs 30, p = 0.053), and hours of dialysis (5.6 hrs vs 3.6 hrs, p = 0.013). There was no relation of either frequency or volume of peritoneal dialysis exchanges to gestational age or fetal survival. CONCLUSIONS: Greater attention to a high intake of protein (>1.5 g/kg) and higher dose of hemodialysis, achieved by longer, every other day dialysis, may be the optimal approach to pregnant patients on hemodialysis. Our first attempt to define the goal of hemodialysis is to keep the predialysis creatinine below 600 mmol/L and the protein intake high enough so the predialysis BUN level is >25 mmol/L. There are no clear guidelines on how to best perform CAPD.

Analysis of Variance↗