The impact of regular hospitalization of children living with thalassaemia on their parents in Sri Lanka: a phenomenological study

This paper reports on a small phenomenological study that set out to describe what it means to have a child with thalassaemia regularly attending hospital for blood transfusion. Ten parents were invited to participate from the thalassaemia unit of a large hospital in a north-west province of Sri Lanka. Data were collected by in-depth interviews with parents. The participants' experiences are described as they reveal, in their own words, what it means to support children with this disease. With startling reality, this research portrays the problems associated with caring for these children and their regular admission to hospital. Three themes are used to present the participant's experience: worries, medical services, and helping and being helped. The findings of the study show that there have been improvements in the service and treatment of these children in Sri Lanka. However, the lives of the parents are still dire. This research should be useful locally in terms of increasing awareness of thalassaemia and raising the consciousness of Sri Lankan nurses and other health care workers, so that they are more aware of the parents' needs. Although phenomenological research is not generalizable, it is likely that the experience of the parents in this study has similarities throughout the developing world.     

Activity of a recombinant fusion protein between transforming growth factor type alpha and Pseudomonas toxin.

The transforming growth factor type alpha gene has been fused to a modified Pseudomonas toxin gene from which the cell-recognition domain has been deleted. The chimeric gene has been expressed in Escherichia coli, and the chimeric protein, PE40-TGF-alpha, has been highly purified. PE40-TGF-alpha kills cells expressing epidermal growth factor receptors and has little activity against cells with few receptors. This chimeric protein might be useful in treating cancers that contain high numbers of epidermal growth factor receptors.     

The isoprostanes in biology and medicine.

Isoprostanes are a new class of lipids, isomers of the conventional enzymatically derived prostaglandins, which are produced in vivo primarily by a free radical-catalyzed peroxidation of polyunsaturated fatty acids. F2-isoprostanes, isomers of the enzyme-derived prostaglandin F2alpha, are the most studied species, but analogous isomers of other prostaglandins and leukotrienes have been described. Because of their mechanism of formation, specific structural features that distinguish them from other free radical-generated products and chemical stability, they can provide a reliable index for the oxidant component of several diseases in vivo. Consistent data suggest that formation of F2-isoprostanes is altered in a variety of clinical settings putatively associated with oxidant stress. Moreover, measurement of F2-isoprostanes might provide a sensitive biochemical basis for dose-selection in studies of natural and synthetic antioxidants. Finally, some F2-isoprostanes possess potent biological activities in vitro and in vivo, suggesting that they may also act as mediators of the cellular effects of oxidative stress.     

Absence of opiate and histamine H2 receptor-mediated effects of clonidine

The possibility that clonidine might exert some of its effects via opiate or histamine H2 receptors has been suggested from observations in animals and man. We undertook a double-blind, randomized study in six normal subjects, comparing the effects of 0.2 mg intravenous clonidine after pretreatment with 300 mg cimetidine, 0.8 mg naloxone, and saline. There was no attenuation of the hypotension, bradycardia, sedation, inhibition of salivary flow, or reduction in plasma catecholamines after cimetidine and naloxone, but the fall in plasma catecholamines ater clonidine correlated with blood pressure, sedation, and salivary flow, suggesting a central adrenergic mechanism for these effects. It is not known whether cimetidine can cross the blood-brain barrier after short-term dosing. We conclude that in normotensive subjects the short-term effects of intravenous clonidine are probably not mediated by an action at peripheral histamine H2 or central opiate receptors.     

Structural genomic variation in childhood epilepsies with complex phenotypes

A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies.