Comparison of three treatment approaches to decreasing cardiovascular disease risk in nondiabetic insulin-resistant dyslipidemic subjects

The efficacy of fenofibrate (FEN), rosiglitazone (RSG), or a calorie-restricted diet (CRD) to reduce cardiovascular disease risk was compared in 37 overweight/obese insulin-resistant nondiabetic subjects. Insulin sensitivity, fasting lipids and lipoproteins, and postprandial plasma glucose, insulin, free fatty acid, and triglycerides were measured before and after 3 months of treatment with FEN, RSG, or CRD. Weight decreased in the CRD group, but did not change significantly after treatment with either drug. Insulin sensitivity improved significantly in the CRD- and RSG-treated groups, but to a greater extent in those administered RSG, without a significant difference comparing FEN treatment with the CRD. Total cholesterol was significantly lower after FEN and CRD treatment. Fasting plasma triglycerides decreased significantly in the FEN- and CRD-treated groups, but postprandial concentrations decreased in only FEN-treated subjects. Significant decreases in postprandial glucose and insulin were seen in only the RSG- and CRD-treated groups. FEN administration improved dyslipidemia in these subjects without changing insulin sensitivity, whereas insulin sensitivity was enhanced in RSG-treated patients without improvement in dyslipidemia. Weight loss in the CRD group led to improvements in both insulin sensitivity and dyslipidemia, but the change in the former was less than in RSG-treated patients, and improvement in lipid metabolism not as great as with FEN. In conclusion, there did not appear to be 1 therapeutic intervention that effectively treated all metabolic abnormalities present in these patients at greatly increased risk of cardiovascular disease.     

Late outcome of multivessel coronary artery disease after angioplasty or bypass surgery

Background. Results from randomized trials to determine optimal treatment for patients with multivessel coronary disease are not yet available. Thus, the early and late outcomes of 191 PTCA and 221 CABG patients done in 1985-86 were evaluated. Methods and Results. CABG patients selected had more coronary risk factors and more severe coronary artery disease compared to PTCA patients. Comparison of the initial outcome showed that clinical success without major cardiovascular events was similar (93.7% for PTCA vs. 90.0% for CABG; p=n.s.). Five year followup was obtained in 99.0% of PTCA patients and 94.4% of CABG patients. In the PTCA group, 89.8% were alive, 4.8% had sustained an MI, and repeat revascularization was required in 46.8%. In the CABG group, 87.1% were alive, 3.2% had had a MI, and 3.5% required repeat revascularization. Statistical comparison demonstrated no difference between the groups in survival or late cardiac events, but rate of repeat revascularization was significantly higher for PTCA patients (p less than 0.0001). Incompleteness of revascularization (p<0.01) was independently associated with an increased need for repeat revascularization in the PTCA group. In the CABG group, depressed left ventricular function (p less than 0.001) and female sex (p<0.01) were associated with lower survival rates. An analysis of cost per patient showed that the strategies were comparable. Conclusions. PTCA and CABG in multivessel disease patients have similar early results and comparable rates of survival and late cardiac events. Significantly more repeat revascularization is required in PTCA patients to maintain these results.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-dose immunosuppression to prevent death after paraquat self-poisoning – a randomised controlled trial

Context: Intentional self-poisoning with the herbicide paraquat has a very high case-fatality and is a major problem in rural Asia and Pacific.

Objectives: We aimed to determine whether the addition of immunosuppression to supportive care offers benefit in resource poor Asian district hospitals.

Materials and methods: We performed a randomised placebo-controlled trial comparing immunosuppression (intravenous cyclophosphamide up to 1?g/day for two days and methylprednisolone 1?g/day for three days, and then oral dexamethasone 8?mg three-times-a-day for 14 days) with saline and placebo tablets, in addition to standard care, in patients with acute paraquat self-poisoning admitted to six Sri Lankan hospitals between 1st March 2007 and 15th November 2010. The primary outcome was in-hospital mortality.

Results: 299 patients were randomised to receive immunosuppression (147) or saline/placebo (152). There was no significant difference in in-hospital mortality rates between the groups (immunosuppression 78 [53%] vs. placebo 94 [62%] (Chi squared test 2.4, p?=?.12). There was no difference in mortality at three months between the immunosuppression (101/147 [69%]) and placebo groups (108/152 [71%]); (mortality reduction 2%, 95% CI: ?8 to +12%). A Cox model did not support benefit from high-dose immunosuppression but suggested potential benefit from the subsequent two weeks of dexamethasone.

Conclusions: We found no evidence that high dose immunosuppression improves survival in paraquat-poisoned patients. The continuing high mortality means further research on the use of dexamethasone and other potential treatments is urgently needed.     

Deconvoluting the dual hypoglycemic effect of wedelolactone isolated from Wedelia calendulacea: investigation via experimental validation and molecular docking

Wedelia calendulacea has a long history of use in the Indian Ayurvedic System of Medicine for the treatment, prevention, and cure of a diverse range of human diseases such as diabetes obesity, and other metabolic diseases. A wide range of chemical constituents, such as triterpenoid saponin, kauren diterpene, and coumestans, has been isolated from the plant. Conversely, no published literature is available in relation to the isolation of wedelolactone (WEL) for its anti-diabetic effect. The aim of the present study was to isolate the bioactive phyto-constituent from Wedelia calendulacea and to scrutinize the antidiabetic effect with its possible mechanism of action. The structure of the isolated compound was elucidated by different spectroscopy techniques. Proteins, such as dipeptidyl peptidase-4 (DPPIV), glucose transporter 1 (GLUT1), and peroxisome proliferator-activated receptors-γ (PPARγ), were also subjected to in silico docking. Later, this isolated compound was scrutinized against α-glucosidase and α-amylase enzyme activity along with an oral glucose tolerance test (OGTT) for estimation of glucose utilization. Streptozotocin (STZ) was used for the induction of type II diabetes mellitus (DM) in Wistar rats. The rats were divided into different groups and received the WEL (5, 10, and 20 mg kg⁻¹, b.w.) and glibenclamide (2.5 mg kg⁻¹, b.w.) for 28 days. The blood glucose level (BGL), plasma insulin, and body weight were determined at regular time intervals. The serum lipid profile hypolipidemic effect for the different antioxidant markers and hepatic tissue markers were scrutinized along with an inflammatory mediator to deduce the possible mechanism. With the help of spectroscopy techniques, the isolated compound was identified as wedelolactone. In the docking study, WEL showed docking scores of −6.17, −9.43, and −7.66 against DPP4, GLUTI, and PRARY, respectively. WEL showed the inhibition of α-glucosidase (80.65%) and α-amylase (93.83%) and suggested an effect on postprandial hyperglycemia. In the OGTT, WEL significantly (P < 0.001) downregulated the BGL, a marker for better utilization of drugs. In the diabetes model, WEL reduced the BGL and enhanced the plasma insulin and body weight. It also significantly (P < 0.001) modulated the lipid profile; this suggested an anti-hyperlipidemia effect. WEL significantly (P < 0.001) distorted the hepatic tissue, acting as an antioxidant marker in a dose-dependent manner. WEL significantly (P < 0.001) downregulated the C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) level. On the basis of the available results, we can conclude that WEL can be an alternative drug for the treatment of type II DM either by inhibiting the production of inflammatory mediator or by the downregulation of oxidative stress.

Wedelia calendulacea has a long history of use in the Indian Ayurvedic System of Medicine for the treatment, prevention, and cure of a diverse range of human diseases such as diabetes obesity, and other metabolic diseases.     

Selectivity of calcium antagonistic action in vascular smooth muscle

Various mechanisms can account for selective inhibition by calcium influx blocking drugs of smooth muscle contractile activity. Diltiazem inhibits calcium influx activated by membrane depolarization as well as alpha adrenergic receptor stimulation. Diltiazem does not inhibit intracellular calcium release nor cause net calcium extrusion up to concentrations of 10(-5) M. As with other calcium influx blocking agents, diltiazem is a potent inhibitor for modes of activation that depend entirely on the presence of extracellular calcium. The calcium influx was found to be mediated by at least three different pathways: one activated by depolarization and highly sensitive to D-600, a second activated by norepinephrine and less sensitive to D-600, and a third "passive leak," that is insensitive to D-600 and accounts for calcium permeability in the resting state. Molecular differences among these various calcium channels may provide the basis for specificity of action of the calcium influx blocking agents.     

Methods for quantifying insulin resistance in human immunodeficiency virus-positive patients

Various indirect indices have been used in human immunodeficiency virus (HIV)-infected individuals to assess insulin resistance, but the validity of these measures has not been rigorously assessed by comparison with physiologic methods of quantifying insulin-mediated glucose uptake (IMGU). We directly measured IMGU in 50 nondiabetic HIV-positive subjects by determining the steady-state plasma glucose (SSPG) concentration in response to a 3-hour continuous infusion of insulin, glucose, and somatostatin. Because steady-state plasma insulin concentrations were similar (approximately 60 microU/mL) in all subjects, the SSPG concentrations provided direct assessments of insulin action. Relationships between SSPG levels and various surrogate measures of IMGU derived from the 75-g oral glucose tolerance test (OGTT) were determined. The indirect measure of IMGU most closely related to SSPG concentrations was the total integrated insulin response to a 75-g glucose load (r=0.78, P<.01), accounting for approximately two thirds of the variability in SSPG (r2=0.61). Other indirect measures of IMGU, including the homeostasis assessment for insulin resistance (HOMA-IR), were also significantly related to SSPG values, but had lower magnitudes of correlation (r=0.43 to 0.61), thereby possessing limited ability to predict SSPG variability (r2=0.18 to 0.37). In conclusion, indirect measures of IMGU need to be applied with caution when evaluating insulin action in HIV-infected patients.     

Effect of bivalirudin on length of stay in the recovery area after percutaneous coronary intervention compared with heparin alone, heparin + abciximab, or heparin + eptifibatide

Three hundred nine patients were followed during their recovery area stay after percutaneous coronary intervention. Recovery area times for patients who received bivalirudin during percutaneous coronary intervention showed an average reduction in total recovery area length of stay of 36 minutes (p <0.0001) compared with patients who received heparin alone. This reduction was also seen when compared with the heparin + abciximab group (46-minute reduction, p = 0.0007), and the heparin + eptifibatide group (35-minute reduction, p = 0.0005). Patients who received bivalirudin took significantly less time for the activated clotting time (ACT) to normalize despite significantly higher average ACTs and significantly fewer subtherapeutic ACTs.     

An analysis of the continuing professional development needs of radiographers and radiation therapists in Singapore

IntroductionContinuing Professional development (CPD) is deemed essential for the Radiographers (DR) and Radiation Therapists (RT) after Singapore commenced state registration. Diagnostic imaging and radiotherapy treatment services are constantly revolutionizing and those working in this field requires sufficient knowledge of the uptrends for training and development. The purpose of this survey is to identify the current training needs of the registered DR and RT in Singapore, and to understand their views about CPD activities.MethodsAn online questionnaire was disseminated by the Singapore Society of Radiographers (SSR) to all registered DR and RT in Singapore, and all practicing in restructured and private hospitals were included. Data collection took place from January 2018 to April 2018.Results102 responses were analysed, where 89 were DR and 13 were RT. CPD was provided in 72.5% (n = 74) of the participants’ institutions, and 69.6% (n = 71) of participants were aware of CPD. Interestingly, participants were significantly more likely to be unaware of CPD when working in an institution which do not offer CPD. Training programme objective was the most important factor for selecting a programme. 93.1% (n = 95) preferred SSR to support them for CPD. There were a few constraints to CPD engagements identified such as financial factors, lack of time, and institution availability.ConclusionThere was significant intrinsic motivation in a quality CPD activity. CPD activities should be current, accessible and relevant for the healthcare professionals to increase participation, which directly contributes to high standards of clinical care.Implications for practiceLocal healthcare institutions should be aware and address needs, gaps and aspirations of the local DR and RT community to ensure adequate preparation has been made upon initiation of mandatory CPD.