Dengue virus is one of the most widespread flaviviruses that re-emerged throughout recent decades. The progression from mild dengue to severe dengue (SD) with the complications such as vascular leakage and hemorrhage increases the fatality rate of dengue. The pathophysiology of SD is not entirely clear. To investigate potential biomarkers that are suggestive of pathogenesis of SD, a small panel of serum samples selected from 1 healthy individual, 2 dengue patients without warning signs (DWS-), 2 dengue patients with warning signs (DWS+), and 5 patients with SD were subjected to a pilot analysis using Sengenics Immunome protein array. The overall fold changes of protein expressions and clustering heat map revealed that PFKFB4, TPM1, PDCL3, and PTPN20A were elevated among patients with SD. Differential expression analysis identified that 29 proteins were differentially elevated greater than 2-fold in SD groups than DWS- and DWS+. From the 29 candidate proteins, pathways enrichment analysis also identified insulin signaling and cytoskeleton pathways were involved in SD, suggesting that the insulin pathway may play a pivotal role in the pathogenesis of SD.
The fresh frozen plasma (FFP) is frequently prescribed either for therapeutic or prophylactic transfusion. The international normalised ratio (INR) value of 1.50 and above is frequently reported to be a transfusion trigger for FFP prior to interventional procedure. This study aimed to evaluate the efficacy of prophylactic FFP transfusion in normalising the INR and to determine the post-transfusion outcomes. Methods: A prospective cross-sectional study involved 81 patients who received prophylactic FFP transfusion over a period of three months. All demographic, clinical data and outcomes of FFP transfusion were captured and filled in the research proforma. Results: The proportion of patients achieved posttransfusion INR below 1.51 was 30.30% (n=27). The majority of patients underwent the interventional procedures with posttransfusion INR > 1.50 (n=52) without experiencing any bleeding episodes. Overall, FFP transfusion resulted in significant median INR difference from 1.89 (IQR, 0.53) to 1.60 (IQR, 0.25); p< 0.001. The greater median INR difference was observed in group with pretransfusion INR > 2.00 and who received FFP doses between 10.00 to 20.00 ml kg-1 (p < 0.001). The INR difference showed the significant, positive correlation with pretransfusion INR values (rs= 0.83, p < 0.001) and FFP doses (rs= 0.72, p< 0.001). Conclusions: The interventional procedures were safely carried out despite abnormal posttransfusion INR. The prophylactic FFP transfusions could be avoided in patients with mild coagulopathy (INR 1.50 - 2.00) prior interventional procedures.
According to literature, the presence of concomitant diabetes mellitus type 2 (DM) is associated with a high frequency of complications in patients with acute myocardial infarction (MI) due to the development of repeated episodes of myocardial ischemia, left ventricular dysfunction, life threatening rhythm disorders, and thromboembolic events Aim: to analyze the state of immuno-inflammation based on the study of calprotectin, as well as to assess the presence and nature of links with carbohydrate metabolism parameters based on the study of blood glucose, insulin and insulin resistance. Patients with AMI in combination with DM 2 were found to have a significant increase in the level of calprotectin by 25.9% (p<0.001) compared to patients with AMI without DM 2. Assessment of carbohydrate metabolism rates revealed changes in the form of statistically significant increase in the concentration of fasting glucose in patients with AMI in combination with DM 2 by 41.8% (p<0.001) when compared to patients with isolated AMI. As for serum insulin, the level of this parameter when combined with the course of AMI and DM 2 significantly exceeded those in patients with AMI without DM 2. The level of HOMA index in patients with AMI with concomitant DM 2 when compared to patients with isolated AMI was also higher (differences are statistically significant, p<0.01). The study showed a correlation between serum calprotectin and insulinemia (R=0.57; p<0.05), HOMA index (R=0.52; p<0.05), fasting glycemia (R=0.59; p<0.05) and troponin I level (R=0,64; p<0,05). The obtained results indicate that the growth of immune inflammatory activity due to the proinflammatory parameter of calprotectin is accompanied by an increase in changes in carbohydrate homeostasis in the form of an increase in the degree of insulin resistance in patients with AMI and DM 2, and severity of cardiac ischemia.
Hypertension professionals from Asia have been meeting together for the last decade to discuss how to improve the management of hypertension. Based on these education and research activities, the Hypertension, brain, cardiovascular and renal Outcome Prevention and Evidence in Asia (HOPE Asia) Network was officially established in June 2018 and includes experts from 12 countries/regions across Asia. Among the numerous research and review papers published by members of the HOPE Asia Network since 2017, publications in three key areas provide important guidance on the management of hypertension in Asia. This article highlights key consensus documents, which relate to the Asian characteristics of hypertension, home blood pressure monitoring (HBPM), and ambulatory blood pressure monitoring (ABPM). Hypertension and hypertension-related diseases are common in Asia, and their characteristics differ from those in other populations. It is essential that these are taken into consideration to provide the best opportunity for achieving "perfect 24-hour blood pressure control", guided by out-of-office (home and ambulatory) blood pressure monitoring. These region-specific consensus documents should contribute to optimizing individual and population-based hypertension management strategies in Asian country. In addition, the HOPE Asia Network model provides a good example of the local interpretation, modification, and dissemination of international best practice to benefit specific populations.
Researches have proved that increasing level of prostate-specific antigen (PSA) is an indicator for the progression of prostate cancer. The present study was focused to determine the PSA level by using anti-PSA antibody conjugated iron oxide nanoparticles, as the probe immobilized on the gap-fingered electrode sensing surface. The detection limit and sensitivity were found at the level of 1.9 pg/mL on the linear regression curve (y = 1.6939x - 0.5671; R² = 0.9878). A dose-dependent liner range was found from 1.9 until 60 pg/mL. Further, PSA was spiked in human serum and did not affect the interaction of PSA and its antibody. This method of detection quantifies the level of PSA, which helps to diagnose prostate cancer at its earlier stage.
A method is described for the determination of pyronaridine in plasma using high-performance liquid chromatography with fluorescence detection. The method involves liquid-liquid extraction with phosphate buffer (pH 6.0, 0.05 M) and diethyl ether-hexane (70:30%, v/v) and chromatographic separation on a C18 column (Nucleosil, 250 x 4.6 mm I.D., 5 microns particle size) with acetonitrile-0.05 M phosphate buffer pH 6.0 (60:40%, v/v) as the mobile phase (1 ml/min) and detection by fluorescence (lambda ex = 267 nm, lambda em = 443 nm). The detector response is linear up to 1000 ng and the overall recoveries of pyronaridine and quinine were 90.0 and 60.3%, respectively. The assay procedure was adequately sensitive to measure 10 ng/ml pyronaridine in plasma samples with acceptable precision (< 15% C.V.). The method was found to be suitable for use in clinical pharmacological studies.
Autoantibodies have been known to be detected during pregnancy. The occurrence of autoantibodies during pregnancy was studied in a group of 146 healthy pregnant women from Jan-March 1995. Serum samples were tested for antinuclear (ANA), anti-ds DNA, anti-mitochondrial, anti-smooth muscle and anti-parietal cell antibodies employing the technique of indirect immunofluorescence. Sera from 66 non-pregnant women were used as controls. Among the pregnant group, 2 (1.4%) were found to have ANA positivity in comparison to none in the control group. This difference was found to be not statistically significant. Only 1 (0.7%) was positive for anti-mitochondrial antibody in the pregnant group compared to one in the control group (p > 0.05). However, anti-ds DNA, anti-smooth muscle and anti-parietal cell antibodies were not detected in both groups. All those positive for autoantibodies were in their 2nd trimester. When these cases were followed-up at the end of their pregnancy, none had complicated pregnancies nor infant abnormalities. Our findings suggest that (a) the occurrence of autoantibodies in pregnant women was not significantly different from non-pregnant controls and that (b) maternal autoantibodies did not appear to cause complications during pregnancy or infant morbidity.
A simple high-performance liquid chromatographic method was developed for the determination of omeprazole in human plasma. Omeprazole and the internal standard, chloramphenicol, were extracted from alkalinized plasma samples using dichloromethane. The mobile phase was 0.05 M Na2HPO4-ACN (65:35, v/v) adjusted to pH 6.5. Analysis was run at a flow rate of 1.0 ml/min at a detection wavelength of 302 nm. The method was specific and sensitive with a detection limit of 2.5 ng/ml at a signal-to-noise ratio of 4:1. The limit of quantification was set at 5 ng/ml. The calibration curve was linear over a concentration range of 5-1280 ng/ml. Mean recovery value of the extraction procedure was about 96%, while the within and between day coefficient of variation and percent error values of the assay method were all less than 14%.
Two series of Blood Pressure (BP) measurements were carried out to assess the variability in BP following repeated measurements in normotensive individuals. In one series, measurement of BP on three occasions three and seven days apart revealed a significant drop in BP in unaccustomed subjects ('untrained'). In a second series assessing the significance of time-interval between measurements or the number of measurements, it was found that a significant fall in BP occurred over the first four days in 'untrained' individuals, whose blood pressure was measured repeatedly for five consecutive days. A significant positive correlation was evident between the falls in systolic and diastolic pressures and the pressure at first screening. Assessment of the anxiety status revealed a significantly lower state anxiety in 'trained' subjects. It therefore appears that (a) BP in normotensive individuals previously unaccustomed to BP measurements, drops significantly with repeated measurements, (b) the number of measurements seem more important than the time-interval between measurements, (c) the largest falls occur in individuals with high initial pressures and (d) the fall upon repeated measurements may be due to reduced anxiety as familiarity with the procedure makes the subjects comparatively relaxed and less state anxious.
The present findings suggest the possible involvement of an active mechanism for transport of iron to the fetus. In all the 19 subjects studied, the cord serum iron levels tended to be higher (129.2 ± 56.8 ug/100ml) than the maternal serum iron levels (74.0 ± 35.9 ug/100ml) at parturition even in maternal iron deficiency. The significant difference (P< 0.001) between cord serum iron levels and the maternal iron levels shows that an active transport mechanism working against a gradient in favour of the fetus exists. The availability of iron to the fetus appears to be dependent on maternal serum iron levels but not on maternal iron stores. This finding serves to stress the importance of iron supplements in pregnancy. A hypothetical model for iron transfer from maternal circulation to fetal circulation is described.
Coronary atheroma is the principal cause of ischaemic heart disease. Among the factors considered to predispose to atheroma formation is raised plasma cholesterol and although it is regarded as a minor risk factor by some, others see its contribution as one of major importance. Whichever the view, the debate on plasma cholesterol and coronary heart disease (CHD) has long moved out of the exclusive domain of the scientific journal to the public arena and is reflected in the increasing frequency with which doctors are consulted by patients on the subject. The incidence of CHD in South-East Asian countries is also rising. For the practising clinician, the problem resolves itself into deciding if the evidence incriminating plasma cholesterol as a predisposing factor is strong enough, and if it is, what prophylactic and therapeutic steps are of value in reducing the incidence of CH D. An updated and brief review of lipid metabolism and the relationship of lipids to CHD is now necessary in view of the rapid accumulation of data from recent trials and prospective studies.
In vitro glycation of sera dried on water-resistant medium (Parafilm) and on paper were studied by measuring the change of glucose level, fructosamine:total protein ratio, glycated protein concentration and alteration of electrophoretic mobility of sera before and after drying. The results suggested the instability of glucose in dried sera was due to in vitro glycation which was influenced by surface properties of media on which the sera were deposited. A new method for rapid effective in vitro glycation of sera was also proposed.
Matched MeSH terms: Blood Chemical Analysis; Blood Glucose/analysis*
BACKGROUND: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia.
METHODS: We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed.
FINDINGS: Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported.
INTERPRETATION: In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events.
FUNDING: National Medical Research Council, Singapore.
Study site: Hospitals, Singapore; University Malaya Medical Centre (UMMC). Kuala Lumpur, Malaysia
Study protocol: https://clinicaltrials.gov/ct2/show/NCT01030211
Morning surge in blood pressure is an independent cardiovascular risk factor in the middleaged and the elderly. Whether such a surge occurs in young subjects is not known. Eighty normotensive subjects (age: 21.8 ± 1.3 yr) measured their own blood pressure (BP) using an automatic device (Omron HEM-7080,) on going to bed and on waking up, for 2 consecutive days. In contrast to large morning BP surges reported for older age groups, there was much smaller but significant (P
Centrifugation of blood samples to produce platelet-poor plasma is one of the important steps for coagulation testing. Reduction of the time required for specimen processing without affecting quality of results should be ideal for tests which require immediate results. Centrifugation of platelet-poor plasma (3580 rpm) for 15 minutes performed for routine coagulation tests would prolong the turn-around time for an urgent test (30 minutes). This study was done to determine the effect of reducing centrifugation time for routine coagulation tests in order to meet the turn-around time (TAT) for urgent tests. Seventy-nine blood samples sent for routine coagulation tests, were assayed for prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level and platelet counts, using two different centrifugation speed for plasma preparation: centrifugation at 3580 rpm for 15 minutes and rapid centrifugation at 4000 rpm for five minutes. Paired sample t-test showed that there was a significant
difference in the platelet count between the two groups (p=0.001). However, there was no significant difference in the normal APTT (p=0.16), abnormal APTT (p=0.80), abnormal PT (p=0.43) and the results of fibrinogen levels (p=0.36). In conclusion, rapid centrifugation at 4000 rpm for five minutes does not modify results of routine coagulation tests (PT, APTT and fibrinogen). It would be beneficial in providing rapid results for urgent coagulation tests.
Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p