Histamine as a marker for hydroxyl radicals

During inflammation an influx of neutrophils and release of mediators from mast cells (such as histamine) take place. The stimulated neutrophils can produce reactive oxygen species (ROS). One of these ROS is the highly reactive hydroxyl radical (OH.). It would be interesting to be able to quantify the extent of ROS formation. We investigated if histamine which is present at the inflammation site can serve as an endogenous marker for the formation of OH.. We found that histamine after incubation with OH. gave two distinct products in our HPLC system. One of the products gave the same characteristics as the synthesized 2-imidazolone derivative of histamine. This suggests that this derivative will be formed when histamine is incubated with OH.

Clinicians' caseload management behaviours as explanatory factors in patients' length of time on caseloads : a predictive multilevel study in paediatric community occupational therapy

Peer reviewedPublisher PD

LEARN 2 MOVE 0-2 years:effects of a new intervention program in infants at very high risk for cerebral palsy; a randomized controlled trial

Background: It is widely accepted that infants at risk for cerebral palsy need paediatric physiotherapy. However, there is little evidence for the efficacy of physiotherapeutic intervention. Recently, a new intervention program, COPCA (Coping with and Caring for infants with special needs - a family centered program), was developed. COPCA has educational and motor goals. A previous study indicated that the COPCA-approach is associated with better developmental outcomes for infants at high risk for developmental disorders. LEARN 2 MOVE 0-2 years evaluates the efficacy and the working mechanisms of the COPCA program in infants at very high risk for cerebral palsy in comparison to the efficacy of traditional infant physiotherapy in a randomized controlled trial. The objective is to evaluate the effects of both intervention programs on motor, cognitive and daily functioning of the child and the family and to get insight in the working elements of early intervention methods.Methods/design: Infants are included at the corrected age of 1 to 9 months and randomized into a group receiving COPCA and a group receiving traditional infant physiotherapy. Both interventions are given once a week during one year. Measurements are performed at baseline, during and after the intervention period and at the corrected age of 21 months. Primary outcome of the study is the Infant Motor Profile, a qualitative evaluation instrument of motor behaviour in infancy. Secondary measurements focus on activities and participation, body functions and structures, family functioning, quality of life and working mechanisms. To cope with the heterogeneity in physiotherapy, physiotherapeutic sessions are video-recorded three times (baseline, after 6 months and at the end of the intervention period). Physiotherapeutic actions will be quantified and related to outcome.Discussion: LEARN 2 MOVE 0-2 years evaluates and explores the effects of COPCA and TIP. Whatever the outcome of the project, it will improve our understanding of early intervention in children with cerebral palsy. Such knowledge is a prerequisite for tailor-made guidance of children with CP and their families.Trial registration: The trial is registered under NTR1428.</p

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

&lt;p&gt;Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.&lt;/p&gt; &lt;p&gt;Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (&#60;2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).&lt;/p&gt; &lt;p&gt;Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).&lt;/p&gt

Lipoprotein Particle Profiles Mark Familial and Sporadic Human Longevity

BACKGROUND: Genetic and biochemical studies have indicated an important role for lipid metabolism in human longevity. Ashkenazi Jewish centenarians and their offspring have large low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles as compared with control individuals. This profile also coincided with a lower prevalence of disease. Here, we investigate whether this observation can be confirmed for familial longevity in an outbred European population and whether it can be extended to sporadic longevity in the general population. METHODS AND FINDINGS: NMR-measured lipoprotein profiles were analyzed in 165 families from the Leiden Longevity Study, consisting of 340 long-lived siblings (females >91 y, males >89 y), 511 of their offspring, and 243 partners of the offspring. Offspring had larger (21.3 versus 21.1 nm; p = 0.020) and fewer (1,470 versus 1,561 nmol/l; p = 0.011) LDL particles than their same-aged partners. This effect was even more prominent in the long-lived siblings (p < 10(−3)) and could be pinpointed to a reduction specifically in the concentration of small LDL particles. No differences were observed for HDL particle phenotypes. The mean LDL particle sizes in 259 90-y-old singletons from a population-based study were similar to those in the long-lived siblings and thus significantly larger than in partners of the offspring, suggesting that the relevance of this phenotype extends beyond familial longevity. A low concentration of small LDL particles was associated with better overall health among both long-lived siblings (p = 0.003) and 90-y-old singletons (p = 0.007). CONCLUSIONS: Our study indicates that LDL particle profiles mark both familial and sporadic human longevity already in middle age

Gene-Network Analysis Identifies Susceptibility Genes Related to Glycobiology in Autism

The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD), and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD