Differential Gene Expression Changes in Children with Severe Dengue Virus Infections

Dengue virus infection is an impressively emerging disease that can be fatal in severe cases. It is not precisely clear why some patients progress to severe disease whereas most patients only suffer from a mild infection. In severe disease, a “cytokine storm” is induced, which indicates the release of a great number of inflammatory mediators (“cytokines”). Evidence suggested that a balance could be involved between protective and pathologic cytokine release patterns. We studied this concept in a cohort of Indonesian children with severe dengue disease using a gene expression profiling method

Treatment of arterial calcification in patients with chronic limb threatening ischemia with etidronate: protocol of an investigator-initiated multicenter, double blind, placebo-controlled, randomized clinical trial

BACKGROUND: Pathologic studies have shown that in patients with critical limb threatening ischaemia (CLTI) medial arterial calcifications are frequently found and may be responsible for aggravating the disease. These extensive calcifitcations are found not only in arteries of the leg but also in the coronary arteries and the aorta. The progression of these calcifications is fast and they stiffen the vessel wall and may thus increase the cardiovascular risk. Reduction of progression of calcification may not only reduce the burden of CLTI but may also reduce the high residual cardiovascular risk. Medial calcifications have been halted by etidronate in other trials. Its potential to reduce the burden from peripheral vascular disease in CLTI and residual cardiovascular risk remains to be established. METHODS: This is an investigator-initiated multicenter, double blind, placebo-controlled, randomized trial comparing the effects of etidronate versus placebo in patients with CLTI. Subjects will be randomized to either treatment with etidronate for 12 months (cyclical 20 mg/kg for 2 weeks on and 10 weeks off) orally or placebo for 12 months (in a similar routine). The primary endpoint is the change in arterial calcification as quantified by CT-scan. Secondary endpoints are the number of amputations above and below the ankle, mortality, number of vascular interventions and quality of life. DISCUSSION: Up to now, the inert end stage of vascular disease in patients with CLTI, has been considered calcification of vessel walls. We believe there is reason to reverse causation and hypothesize that calcification causes vascular disease. This reversal can be proven in a clinical trial if halting the calcification process improves the outcome of the patient. Therefore we use etidronate, a bisphosphate that has proven to stop the calcification in several rare monogenetic calcifying diseases. We aim to perform this mechanistic proof-of-concept study hopefully leading to a clinical outcome study later on

The Diagnostic Sensitivity of Dengue Rapid Test Assays Is Significantly Enhanced by Using a Combined Antigen and Antibody Testing Approach

Dengue is a serious public health concern with around 3 billion people at risk of infection. Severe forms of the infection can be fatal and with no licensed vaccine or effective therapeutic currently available, early detection is important to assist with the clinical management of symptoms. Isolation of the virus and the detection of viral RNA using RT-PCR are commonly used methods for early diagnosis but are time-consuming, expensive and require skilled operation. Rapid immunochromatographic tests (ICT) are relatively simple, inexpensive and easy to perform at or near the point of care. Here, we report on the clinical performance of a new rapid ICT for the non-structural protein 1 (NS1) of dengue virus, a marker of acute infection. At two clinical study sites, NS1 was detected in 60–70% of laboratory-confirmed dengue cases and specificity of the test was >95%. We have also shown that a combined testing approach for both circulating NS1 antigen and antibody responses to the glycoprotein E of the virus can significantly improve diagnostic sensitivity compared to the detection of NS1 alone. Importantly, the combined antigen and antibody testing approach also provides an expanded window of detection from as early as day 1 post-onset of illness

Daily Nighttime Melatonin Reduces Blood Pressure in Male Patients With Essential Hypertension

Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function. Recently, the biological clock was shown to be involved in autonomic cardiovascular regulation. Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension. We conducted a randomized, double-blind, placebo-controlled, crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute ( single) and repeated ( daily for 3 weeks) oral melatonin (2.5 mg) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality. Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg, respectively. The treatment did not affect heart rate. The day - night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15% and 25%, respectively. A single dose of melatonin had no effect on blood pressure. Repeated ( but not acute) melatonin also improved sleep. Improvements in blood pressure and sleep were statistically unrelated. In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure. Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake. The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertensio

Low creatine kinase is associated with a high population incidence of fainting

OBJECTIVE: Vasoconstrictor capacity, skeletal muscle tone, and renal sodium retention are involved in the pathogenesis of fainting. As muscle contractility and ion transport are highly energy-demanding processes, we hypothesized that a low activity of the energy-generating enzyme creatine kinase (CK) is associated with a higher risk of fainting. The aim of this observational study was to explore the association of vasovagal syncope with low CK. METHODS: A random sample of 1,000 subjects aged 34–60 years was drawn from the general population, with 442 subjects eventually included in the study. Data on fainting history were collected with the investigators blinded to participants’ CK level. We prepared this report according to the “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) statement. The main outcome was the lifetime cumulative incidence of vasovagal syncope in subjects with low versus high-normal serum CK after a 3 days rest. RESULTS: The proportion of fainters within the high CK group was 29 out of 130 (22%) versus 121 out of 312 (39%) in the low CK group; a 73% greater occurrence of fainting with low CK (P = 0.0005). This finding was consistent across recurrent fainters, and in men and women. INTERPRETATION: Low CK is associated with a 73% higher incidence of fainting in a random population sample. The association is biologically plausible, as CK enhances cardiovascular and skeletal muscle contractility and salt retention. The presented data suggest that low CK activity is a potential new risk factor for vasovagal syncope