Iron-balance and dose-response studies of the oral iron chelator 1,2- dimethyl-3-hydroxypyrid-4-one (L1) in iron-loaded patients with sickle cell disease

Several life-threatening complications of the common disorder sickle cell disease require management with red blood cell transfusions and, hence, long-term iron-chelating therapy. The efficacy of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) has not previously been determined in patients with sickle cell disease. We compared the efficacy of L1 to that of standard-dose subcutaneous deferoxamine in four regularly transfused patients with homozygous sickle cell disease, who had evidence of severe iron overload and a history of poor compliance with deferoxamine. Determination of 24-hour urinary iron excretion conducted over 5 days immediately after transfusion showed that the mean daily urinary iron excretion induced by L1 at 75 mg/kg/d (0.48 +/- 0.23 mg/kg) was equivalent to that induced by deferoxamine at 50 mg/kg/d (0.39 +/- 0.06 mg/kg). In two of three patients studied, a significant (P < .025) increase in mean daily urinary iron excretion was achieved when the dose of L1 was increased to 100 mg/kg/d. Total iron balance studies, which quantitated both urinary and stool iron excretion on L1 and deferoxamine, determined that mean total daily iron excretion induced by deferoxamine (0.88 +/- 0.05 mg/kg) was significantly greater (P < .05) than that induced by L1 (0.53 +/- 0.17 mg/kg), attributable to the significantly greater stool iron excretion during deferoxamine treatment (0.50 +/- 0.16 mg/kg/d) compared with that measured during L1 treatment (0.12 +/- 0.08 mg/kg/d, P < .01). Stool iron excretion accounted for a significantly greater percentage of total iron excretion during deferoxamine treatment (59% +/- 20%) than during L1 treatment (23% +/- 14%, P < .01). These iron balance studies are the first to compare total iron excretion induced by L1 with that achieved by deferoxamine. They demonstrate that the mean total daily iron excretion during L1 treatment (0.53 +/- 0.17 mg/kg) is sufficient to maintain net negative iron balance in most regularly transfused patients with sickle cell disease. Because long-term compliance with L1 has been shown previously to be superior to that with deferoxamine in patients with homozygous beta-thalassemia, the use of L1 should increase the long-term effectiveness of iron chelation in patients with sickle cell disease.     

HIV in central and eastern Europe

We describe recent trends in the HIV epidemic and the differences between eastern and central Europe, using surveillance data, and published and unpublished reports. During the past 5 years, most countries of the former Soviet Union have been severely affected by HIV epidemics that continue to spread as a result of injecting drug use. With an estimated 1 million individuals already infected--mostly injecting drug users--and high rates of syphilis, the region may soon also face a large-scale epidemic of sexually-transmitted HIV infection. Indeed, data indicate that an HIV epidemic, fuelled by heterosexual transmission, is emerging; its expansion will depend on the size of so-called bridge populations that link high-risk groups with the general population. The lack of evidence to indicate increased rates of HIV as a result of homosexual transmission could indicate the social vulnerability of homosexual and bisexual men in the region rather than the true epidemiological picture. In view of the current levels of HIV prevalence, eastern Europe will soon be confronted with a major AIDS epidemic. By contrast, rates of HIV in central Europe remain low at present, but behaviours that promote HIV transmission are present in all countries. Improved measures to prevent further HIV spread are urgently needed.     

Relationship between interleukin-1 type 1 and 2 receptor gene polymorphisms and the expression level of membrane-bound receptors

The biological activity of the multifunctional cytokine interleukin-1 (IL-1) is mediated by its receptors. The aim of this study was to determine if an association exists between single nucleotide polymorphisms (SNPs) in the IL-1 type 1 and 2 receptor genes (IL1R1 and IL1R2) and the expression level of membrane-bound IL1Rs on subpopulations of mononuclear cells or serum levels of soluble IL-1 receptors. It was observed that healthy individuals with the genotype TT in SNP rs2234650:C>T had a lower percentage of intact CD14⁺ monocytes expressing IL1R1 on their surface. The SNP rs4141134:T>C in IL1R2 has also been associated with the percentage of intact CD3⁺ T cells expressing IL1R2. Furthermore, individuals carrying the CC allele of SNP rs4141134:T>C and the TT allele of SNP rs2071008:T>G in IL1R2 had a lower density of IL1R2s on the surface of CD14⁺ monocytes in lipopolysaccharide (LPS)-stimulated PBMC cultures. In summary, this study demonstrated that IL-1 receptor gene polymorphisms could be one of the factors influencing the expression of membrane-bound IL-1 receptors (IL1R) on immunocompetent cells.     

Early warning indicators for population-based monitoring of HIV drug resistance in 6 African countries

Human immunodeficiency virus (HIV) RNA testing and HIV drug resistance (HIVDR) testing are not routinely available for therapeutic monitoring of patients receiving antiretroviral therapy (ART) in resource-limited settings. World Health Organization HIVDR early warning indicators (EWIs) assess ART site factors known to favor the emergence of HIVDR. HIV drug resistance EWI monitoring was performed within the PharmAccess African Studies to Evaluate Resistance Monitoring (PASER-M) study, comprising 13 ART sites in 6 African countries. Early warning indicator assessment in the PASER network identified vulnerable aspects of ART programs and triggered interventions aimed at minimizing HIVDR emergence. Additionally, data suggest an advantage of medication possession ratio over on-time antiretroviral drug pickup in identifying patients at risk for HIVDR development.     

Use of physical restraints with cognitively impaired nursing home residents

AIM: The aim of the study was to examine the prevalence of physical restraint use in cognitively impaired nursing home residents, the manner in which restraints are used, reasons for using them, and relationships between residents' characteristics and use of physical restraints. METHODS: A point prevalence study was conducted on the use of physical restraints among all residents cared for in two Dutch nursing homes and one nursing home unit (n = 265). Data about the nursing home residents and the use of restraints were collected by means of a questionnaire, which was filled in by the nurses. The response rate was 98%. The mean age of residents was 81 years (sd = 8.6), 74% of whom were female. RESULTS: One or more restraints were used with 49% of the residents. The most frequently used physical restraints were bed rails, a waist belt, and a chair with a table. In almost all situations (90%), residents were continuously restrained and restraints were used for longer than 3 months. The most common reason (90%) for use of restraints was to prevent falls. Logistic regression analysis revealed that use of restraints was highly associated with poor mobility, care dependency and risk of falling in the opinion of nursing staff. CONCLUSIONS: The results of this study are comparable with those of other studies. However, since recent studies have reported that physical restraints are inadequate to prevent falls, recommendations are made to re-evaluate critically the use of restraints and to conduct future research into a responsible and safe way of decreasing the use of physical restraints.     

The efficacy of non-pharmacological interventions in the management of pain in preterm and term neonates. A systematic literature review

Many diagnostic and therapeutic procedures performed in the neonatal intensive care unit are painful for the preterm or term infant. Pain is therefore a central issue in neonatal intensive care nursing. As significant side effects are associated with analgesics, non-pharmacological methods of pain prevention and relief are being favoured over pharmacological therapy. This development is very important for the nursing profession since non-pharmacological interventions are determined and carried out without an order from a physician. This review of the current literature investigates the efficacy of non-pharmacological nursing interventions in the management of pain in the neonatal intensive care unit. Despite certain methodological problems with some of the studies included in this review, the trend favours non-pharmacological interventions. Modulation of arousal and excitability during and after a painful stimulus as well as an effect on physiological and behavioural parameters have been described following non-pharmacological interventions. The studies reviewed suggest that neonates show fewer signs of pain and stress after non-pharmacological interventions for prevention and relief of pain.     

Development of a PPRV challenge model in goats and its use to assess the efficacy of a PPR vaccine

Peste des Petits Ruminants (PPR) is a severe disease of small ruminants and has high economic impacts in developing countries. Endemic in Africa, the Middle East and Asia, the disease is currently progressing with occurrences reported in North Africa, Turkey and in Georgia, and now threatens Europe. Much remains unknown about the infection dynamics, the virulence of the different strains and species/breed susceptibility. Robust experimental challenge models are needed to explore these fields and to confirm the efficacy of currently sold vaccines. We first assessed virulence of two PPR virus strains (CI89 and MA08) in Saanen goats. Whereas the MA08 strain led to classical severe clinical signs of PPR, the CI89 strain appeared to cause a mild disease in Saanen goats, highlighting the difference in virulence between strains in this animal model. We further demonstrated the importance of the inoculation route in the appearance of clinical signs and that ocular excretion is a better choice than blood for viral detection. After developing a robust challenge model, we assessed the efficacy of a vaccine (PPR-VAC®, BVI Botswana) against the MA08 strain and demonstrated that this vaccine blocked viral excretion and significantly reduced clinical signs. These results reinforce the paradigm that a strain from one lineage could protect against strains from other lineages.