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Biomedical subjects

K Ng

Publications and source records attributed to K Ng.

At least 19 recordsLinked to original sources

B-type natriuretic peptide levels are not a surrogate marker for invasive hemodynamics during management of patients with severe heart failure.

BACKGROUND: We sought to assess the utility of serial BNP measurements in patients with severe heart failure and attempted to correlate values with invasively derived data. METHODS: In a retrospective study, we analyzed serial BNP levels in patients receiving hemodynamically guided therapy for severe heart failure and sought correlation with invasively derived data. RESULTS: Thirty-nine patients with New York Heart Association Class III-IV, with an ejection fraction of 35% or less, who had a pulmonary artery catheter inserted for hemodynamically tailored heart failure therapy, were identified and serial BNP measurements reviewed. BNP was estimated on admission, at 12 and 36 hours. Normally distributed variables are expressed as mean +/- SD and otherwise as median +/- interquartile range. Mean ejection fraction was 16% +/- 6%. Mean pulmonary artery occlusion pressures (PAOP) fell with therapy and were 25 +/- 7 mmHg, 18 +/- 7 mmHg and 19 +/- 7 mmHg at admission, 12 hours and 36 hours respectively ( P < 0.05). Median BNP levels fell from 1200 +/- 641 to 771 +/- 803 at 12 hours and to 805 +/- 771 at 36 hours (P < .001). There was no correlation between BNP and any hemodynamically derived variable. A change in BNP was not associated with a change in PAOP in any individual patient. Only 42% remained alive on medical therapy at 30 days. CONCLUSIONS: In patients with severe heart failure, BNP levels do not accurately predict serial hemodynamic changes and do not obviate the need for pulmonary artery catheterization.

Adult↗

The effects of body weight on airway calibre.

Increased wheeze and asthma diagnosis in obesity may be due to reduced lung volume with subsequent airway narrowing. Asthma (wheeze and airway hyperresponsiveness), functional residual capacity (FRC) and airway conductance (Gaw) were measured in 276 randomly selected subjects aged 28-30 yrs. Data were initially adjusted for smoking and asthma before examining relationships between weight and FRC (after adjustment for height), and between body mass index (BMI = weight.height(-2)) and Gaw (after adjustment for FRC) by multiple linear regression, separately for females and males. For males and females, BMI (+/-95% confidence interval) was 27.0+/-4.6 kg.m(-2) and 25.6+/-6.0 kg.m(-2) respectively, Gaw was 0.64+/-0.04 L.s(-1).cmH2O(-1) and 0.57+/-0.03 L.s(-1).cmH2O(-1), and FRC was 85.3+/-3.4 and 84.0+/-2.9% of predicted. Weight correlated independently with FRC in males and females. BMI correlated independently and inversely with Gaw in males, but only weakly in females. In conclusion, obesity is associated with reduced lung volume, which is linked with airway narrowing. However, in males, airway narrowing is greater than that due to reduced lung volume alone. The mechanisms causing airway narrowing and sex differences in obesity are unknown.

Adult↗

Spinal versus epidural anaesthesia for caesarean section.

BACKGROUND: Regional anaesthesia (spinal or epidural anaesthesia) for caesarean section is the preferred option when balancing risks and benefits to the mother and her fetus. Spinal anaesthesia for caesarean section is thought to be advantageous due to simplicity of technique, rapid administration and onset of anaesthesia, reduced risk of systemic toxicity and increased density of spinal anaesthetic block. OBJECTIVES: To assess the relative efficacy and side-effects of spinal versus epidural anaesthesia in women having caesarean section. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Trials Register (February 2003) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003). SELECTION CRITERIA: Types of studies considered for review include all published randomised controlled trials involving a comparison of spinal with epidural anaesthesia for caesarean section. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion. Review Manager software was used for calculation of the treatment effect represented by relative risk (RR) and weighted mean difference (WMD) using a random effects model with 95% confidence intervals (CI). MAIN RESULTS: Ten trials (751 women) met our inclusion criteria. No difference was found between spinal and epidural techniques with regards to failure rate (RR 0.98, 95% CI 0.23 to 4.24; four studies), need for additional intraoperative analgesia (RR 0.88, 95% CI 0.59 to 1.32; five studies), need for conversion to general anaesthesia intraoperatively, maternal satisfaction, need for postoperative pain relief and neonatal intervention. Women receiving spinal anaesthesia for caesarean section showed reduced time from start of the anaesthetic to start of the operation (WMD 7.91 minutes less (95% CI -11.59 to -4.23; four studies), but increased need for treatment of hypotension RR 1.23 (95% CI 1.00 to 1.51; six studies). REVIEWERS' CONCLUSIONS: Both spinal and epidural techniques are shown to provide effective anaesthesia for caesarean section. Both techniques are associated with moderate degrees of maternal satisfaction. Spinal anaesthesia has a shorter onset time, but treatment for hypotension is more likely if spinal anaesthesia is used. No conclusions can be drawn about intraoperative side-effects and postoperative complications because they were of low incidence and/or not reported.

Anesthesia, Epidural↗

Massive pulmonary haemorrhage complicating the treatment of acute coronary syndrome.

Antiplatelet medications such as clopidogrel and tirofiban (glycoprotien IIb/IIIa inhibitors) are associated with a reduction in mortality and morbidity and are therefore recommended in the treatment of acute coronary syndromes. Massive pulmonary haemorrhage is a rare complication of both clopidogrel and tirofiban. Pulmonary haemorrhage may easily be mistaken for acute pulmonary oedema, a condition commonly seen in patients with acute coronary syndrome. Physicians need to be aware of this diagnostic dilemma because early treatment increases the chances of patient survival.

Angina, Unstable↗

Effects of gas and other fume emitting heaters on the development of asthma during childhood.

BACKGROUND: Several studies have shown adverse effects of gas cookers and heaters on respiratory health. The long term effects of early life exposure to these appliances are not known. This study investigated the effect of exposure to fume emitting heaters, currently and during the first year of life, on the risk of asthma outcomes. METHODS: A cross sectional study of schoolchildren (n = 627) aged 8-11 years was conducted in Belmont, Australia. Information on symptoms and heating types was collected by parent completed questionnaire. Atopy was assessed by skin prick tests and airway hyperresponsiveness (AHR) was assessed by histamine challenge test. RESULTS: There was no association between the current use of fume emitting heaters and any of the asthma outcomes. However, having been exposed to fume emitting heaters during the first year of life was associated with an increased risk of having AHR (relative risk (RR) 1.47, 95% confidence interval (CI) 1.06 to 2.03), recent wheeze (RR 1.44, 95% CI 1.11 to 1.86), and recent wheeze + AHR (RR 2.08, 95% CI 1.31 to 3.31). CONCLUSION: If confirmed in other settings, this finding would require a review of the range of heating types that are appropriate for use in households in which young children live.

Air Pollution, Indoor↗

Dense middle cerebral artery sign: a pictorial study.

The hyperdense middle cerebral artery on computed tomography (CT), although a useful sign of middle cerebral artery occlusion, does not presage the events to follow. Because of the wide availability of CT it is useful to illustrate the radiological spectrum of findings following middle cerebral artery occlusion. This is pictorial study of four prototypic patients with hyperdense middle cerebral artery which was the common denominator. There was a marked heterogeniety among the patients in relation to the character of the vascular disturbances, location, extent of ischaemic changes and the final outcome. We emphasise that a single radiological sign should be seen in the context of the entire scan.

Adult↗

Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results.

BACKGROUND AND PURPOSE: A previous trial (the Clomethiazole Acute Stroke Study) generated the hypothesis that clomethiazole is effective in patients with a major ischemic stroke (total anterior circulation syndrome), and this was tested in the present study. METHODS: A total of 1198 patients with major ischemic stroke and a combination of limb weakness, higher cortical dysfunction, and visual field deficits were randomly assigned to clomethiazole (68 mg/kg IV over 24 hours) or placebo. The study drug was initiated within 12 hours of symptom onset. Functional outcome and neurological recovery were assessed at days 7, 30, and 90, with the proportion of patients with a Barthel Index > or =60 at last follow-up as the primary outcome measure. RESULTS: The patients were randomly assigned equally, and the two treatment groups were well matched for baseline characteristics, including stroke severity (mean National Institutes of Health Stroke Scale score 16.9+/-5.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of > or =60 was 42% in the clomethiazole-treated group and 46% in the placebo-treated group (odds ratio, 0.81; 95% CI, 0.62 to 1.05; P=0.11). There was no evidence of efficacy on any secondary outcome variables (modified Rankin Score, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, and 30-day CT infarct volumes) compared with placebo. Subgroup analysis showed a similar lack of treatment effect in patients treated early (<6 hours) and in those treated later (6 to 12 hours). Somnolence was an expected pharmacological effect of clomethiazole, and this occurred during treatment as an adverse event in half of the patients randomly assigned to study drug. CONCLUSIONS: The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke.

Acute Disease↗

A preliminary study of the utility of combined cardiac markers in the evaluation of patients presenting early with suspected acute coronary syndrome.

OBJECTIVE: The aim of the study was to investigate and compare the usefulness and accuracy of various cardiac markers [troponin I, creatine kinase MB (CKMB) mass, creatine kinase (CK), CKMB activity] to aid early diagnosis of myocardial infarction. We also examined the ability of the various cardiac markers to prognosticate future adverse cardiac events. MATERIALS AND METHODS: Patients admitted within 8 hours of maximal chest pain suggestive of acute coronary syndrome with non-diagnostic electrocardiograms were recruited. Blood samples were obtained on admission to the wards and repeated 4 hours later. These results were later correlated to the final hospital discharge diagnosis. RESULTS: The 37 patients in the study were a high-risk population with over 50% presenting with a Thrombolysis in Myocardial Infarction (TIMI) risk score of greater or equal to 3. Myoglobin was the most sensitive marker (100% sensitivity) in early prediction of patients who were subsequently diagnosed to have a myocardial infarction. Patients with an elevated troponin I level but normal CK and myoglobin levels had a significantly higher risk of developing a major adverse clinical event (MACE) within 3 months of the initial presentation. CONCLUSION: Myoglobin is the most sensitive marker when compared to CK, CKMB and troponin I for diagnosing patients presenting early with chest pain and a non-diagnostic electrocardiogram and who subsequently develop either a ST-elevation myocardial infarction or non-ST elevation myocardial infarction. Patients with an elevated troponin I level but normal CK and myoglobin levels are at higher risk of an adverse clinical event.

Adult↗

Acquisition of secondary structural chromosomal changes in pediatric ewing sarcoma is a probable prognostic factor for tumor response and clinical outcome.

BACKGROUND: The Ewing sarcoma (ES) group of tumors commonly have the t(11;22)(q24;q12) or other rearrangements involving 22q12. In addition to these consistent aberrations, both numeric and structural aberrations have been reported: namely gains of chromosomes 8 and 12, the unbalanced translocation t(1;16), and deletions at the short arm of chromosome 1. METHODS: To evaluate the frequency and to study the prognostic implications of some of these aberrations in children, the authors performed a pilot study of 26 ES pediatric patients by classic cytogenetics and/or interphase fluorescence in situ hybridization (FISH) and compared these data with clinical parameters. RESULTS: Gains of chromosomes 8 and 12 were detected, by interphase FISH, in 48% (10 of 21) and 38% (6 of 16) of the tumors, respectively, and this was not significant with respect to treatment response. Statistical analysis revealed that the presence of additional secondary structural chromosomal aberrations was associated with an unfavorable outcome (P = 0.0034 as an independent prognostic value as an unfavorable marker). Presence of metastasis at diagnosis also was found to be associated with poor outcome (P = 0.0131). Spectral karyotyping analysis was shown to facilitate the detection of more complex structural chromosomal aberrations in a representative ES tumor. CONCLUSIONS: It is important to determine whether additional structural chromosomal aberrations are present in ES tumors because it appears that a more complex karyotype with multiple chromosomal aberrations is associated with poor outcome in ES.

Adolescent↗

Quantitative screening and matrix effect studies of drug discovery compounds in monkey plasma using fast-gradient liquid chromatography/tandem mass spectrometry.

A higher-throughput bioanalytical method based on fast-gradient (1 min run time) high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS) was developed for screen-type analyses of plasma samples from early drug discovery studies in support of exploratory pharmacodynamic studies. The HPLC system equipped with minibore column was interfaced with either atmospheric pressure chemical ionization (APCI) or electrospray (ESI) ionization techniques. The matrix ion suppression effect of both quantitative HPLC/MS/MS analyses was compared using the post-column infusion system. The use of the described methods provided advantages such as a shorter chromatographic region of ion suppression, less solvent consumption and shorter run times in comparison with standard analytical column HPLC/MS/MS methods. The analytical results obtained by both HPLC/MS/MS methods were in good agreement (within 15% of error) and displayed a good correlation with the pharmacodynamic outcome.

2-Hydroxypropyl-beta-cyclodextrin↗

Direct simultaneous analysis of plasma samples for a drug discovery compound and its hydroxyl metabolite using mixed-function column liquid chromatography-tandem mass spectrometry.

A polymer-coated mixed-function (PCMF) column was evaluated for direct plasma injection for the simultaneous determination of a drug candidate and its hydroxyl metabolite by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS-MS) in support of pharmacokinetic studies. Each diluted monkey plasma sample containing internal standard was directly injected on to the PCMF column for sample clean-up, enrichment and chromatographic separation. The proteins and macromolecules were first eluted from the column while the drug molecules were retained on the bonded hydrophobic phase. The analytes retained on the column were then eluted with a strong mobile phase using a gradient separation technique at a constant flow rate of 1.0 ml min(-1). When not diverted, the column effluent was connected either to the atmospheric pressure chemical ionization (APCI) source or the electrospray ionization (ESI) source as part of the mass spectrometer system used for quantification. The calibration curve was linear over the range 5-2500 ng ml(-1) for both analytes. The retention times for the analytes and the internal standard were both consistent and no column deterioration was observed for at least 500 injections. The recovery through the column and reproducibility of the dosed compound and its hydroxyl metabolite in monkey plasma samples were > 90% (RSD < 6%). The total analysis time was < 8 min per sample. The analytical results obtained by the proposed direct plasma injection method were in good agreement with those obtained by the conventional LC-MS-MS method.

Chromatography, Liquid↗

Coffee and coronary heart disease.

BACKGROUND: The role of coffee consumption in the onset of myocardial infarction remains uncertain. A review of published reports showed that although cohort data suggest very little excess risk of coronary heart disease among habitual coffee drinkers, case-control data suggest an excess risk of the order of 60% for people drinking five or more cups per day. METHODS: We obtained as much information as possible on the lifestyle and habits, including coffee consumption, of people admitted with chest pain to the Coronary Care Unit at the Royal Perth Hospital, Australia. A questionnaire was given to them by the attending nursing staff. Details were recorded by the patient, often with help from the nursing staff. A similar questionnaire was completed by patients attending the Cardiology Outpatient Clinic. RESULTS: One of the outstanding differences between the 182 patients with myocardial infarction or unstable angina and 185 patients with chronic stable coronary heart disease who filled in forms while waiting in the Cardiology Outpatient Clinic was that more people with acute coronary syndromes were drinking in excess of five cups of coffee per day (18 vs 7.5%; P = 0.003). In logistic regression analysis adjusted for age, smoking status (past and current), hypertension, dyslipidaemia and diabetes, the odds ratio was 2.51 (95% CI 1.43,4.43; P = 0.021). CONCLUSION: The present case-control study provides evidence for an increased risk of myocardial infarction or unstable angina among individuals drinking more than five cups of coffee per day.

Journal Article↗

Assessment of total energy expenditure in a Chinese population by a physical activity questionnaire: examination of validity.

A physical activity questionnaire from which total daily energy expenditure (TEE) could be estimated was developed for adult Hong Kong Chinese subjects, and its reliability and validity examined. The questionnaire was based on questionnaires used in Caucasians, and adapted for local lifestyle after focus group meetings involving subjects of all age groups. The questionnaire was administered to 94 subjects, consisting of healthy adults, the elderly, and two patient groups (those with renal disease on continuous ambulatory peritoneal dialysis and those with cancer). Seventy-one subjects were reinterviewed within 14 days to test reliability. Validity was examined in 31 normal subjects by measuring the basal metabolic rate (BMR) by indirect calorimetry and multiplying by the physical activity level (PAL) obtained from published studies using the doubly labelled water method and also from FAO/WHO/UNU to obtain the TEE. The intraclass correlation coefficient of reliability rages from 0.7 to 0.8 for all subject groups. The mean estimated TEE from the questionnaire was not significantly different from the mean value derived from measured BMR x PAL. The mean bias ranged from an underestimation of 27 kcal to overestimation of 215 kcal. However, the limits of variability were wide. Age was inversely related to the energy expended for occupational activities, but was positively associated with energy expended in leisure activities. Women spent less energy on occupational and exercise activities, and more on caretaking activities. Those with disease were also less likely to participate in caretaking activities. We conclude that this questionnaire may be a useful tool for future studies where energy expenditure needs to be estimated in various settings in the Hong Kong Chinese population.

Aged↗

Impact of early intervention on outcome after mild traumatic brain injury in children.

OBJECTIVE: The impact of mild head injury or mild traumatic brain injury (TBI) in children is variable, and determinants of outcome remain poorly understood. There have been no previous attempts to evaluate the impact of interventions to improve outcome. Results of previous intervention studies in adults have been mixed. This study aimed to evaluate the impact of providing information on outcome measured in terms of reported symptoms, cognitive performance, and psychological adjustment in children 3 months after injury. METHODS: A total of 61 children with mild TBI were assessed 1 week and 3 months after injury, and 58 children with mild TBI were assessed 3 months after injury only. They were compared with 2 control groups (N = 45 and 47) of children with minor injuries not involving the head. Participants completed measures of preinjury behavior and psychological adjustment, postconcussion symptoms, and tests of attention, speed of information processing, and memory. Children with mild TBI seen at 1 week were also given an information booklet outlining symptoms associated with mild TBI and suggested coping strategies. Those seen 3 months after injury only did not receive this booklet. RESULTS: Children with mild TBI reported more symptoms than controls at 1 week but demonstrated no impairment on neuropsychological measures. Initial symptoms had resolved for most children by 3 months after injury, but a small group of children who had previous head injury or a history of learning or behavioral difficulties reported ongoing problems. The group not seen at 1 week and not given the information booklet reported more symptoms overall and was more stressed 3 months after injury. CONCLUSIONS: Providing an information booklet reduces anxiety and thereby lowers the incidence of ongoing problems.

Adaptation, Psychological↗

Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment.

OBJECTIVE: To assess the efficacy and safety of glucagon-like peptide-1 (GLP-1) on the plasma glucose level when given as a continuous infusion for either 16 or 24 h per day to type 2 diabetic patients who were poorly controlled on sulfonylurea treatment. RESEARCH DESIGN AND METHODS: This single-center, randomized, parallel, double-blind, placebo-controlled trial was conducted in 40 hospitalized patients who were randomized to receive infusions of either placebo or GLP-1 4 or 8 ng. kg(-1). min(-1) for either 16 or 24 h per day for 7 days. At predetermined intervals, 24-h profiles of glucose, glucagon, and insulin were measured. Adverse events and clinical chemistry and hematology were recorded. RESULTS: For all active treatment groups, the change in average glucose (area under the curve [AUC] for day 7 minus AUC for day 0 divided by 24 h) was statistically significantly different from placebo (P < or = 0.001). The GLP-1 8 ng. kg(-1). min(-1) dose given for 24 h was more efficacious than any of the other doses (P < or = 0.05). Nocturnal and fasting plasma glucose levels at day 7 were greater in the 16-h groups compared with the 24-h groups (P < or = 0.05). Insulin AUC did not show any treatment effect for any of the treatment groups when change was assessed from day 0 to day 7. However, for the 16-h groups, the pattern of the insulin profiles changed; the insulin profiles were considerably higher during the initial 3-4 h after restart of the GLP-1 infusion on day 7, although there was a tendency for insulin levels to decrease during the afternoon and evening. Glucagon AUC decreased significantly for all active treatment groups compared with placebo. GLP-1 was generally well tolerated. CONCLUSIONS: This study demonstrated that GLP-1 should be given continuously to obtain the most optimal glycemic control. Because of the short plasma half-life of native GLP-1, long-acting derivatives should be developed to make GLP-1 treatment clinically relevant.

Adult↗

Time course analysis and modulating effects of established brain tumor on active-specific immunotherapy.

OBJECT: There have been numerous attempts to establish an effective immunotherapy for the treatment of brain tumors. To date, reliable methods to manipulate the immune system for promoting brain tumor regression have been disappointing. Generation of active immune responses in most of these studies was only possible in the absence of viable tumor cells, suggesting that immunotherapy can only be used as preventive therapy. In few studies the investigators have demonstrated success in using immunotherapy to treat a preestablished intracranial tumor. Using the 9L intracranial glioma model, the authors sought to delineate the underlying mechanisms for these observations. METHODS: In animals vaccinated with irradiated 9L glioma cells and interferon-gamma 14 and 7 days prior to intracranial tumor cell challenge, a significant increase in survival was shown. In contrast, vaccinations applied 3 days prior to, at the time of (Day 0) or 7 days after intracranial tumor cell challenge failed to influence survival. Histological examination of brain tissue specimens obtained in animals vaccinated before or after tumor cell challenge showed no difference in the degree of peritumoral mononuclear cell infiltration. When activated spleen cells obtained obtained from these animals were assayed for cytotoxicity and proliferative capacity, only those spleen cells derived from animals vaccinated prior to intracranial tumor cell challenge showed enhanced activity. CONCLUSIONS: These data support the presence of a strong modulatory effect of tumor on local and systemic antitumoral immune response. This immunosuppression appears to be secondary to a direct effect on T-cell function. Reversal of this immunosuppression may be a useful adjunct to tumor vaccine therapy.

Animals↗