Euthanasia and assisted suicide in the Netherlands: Clarifying the practice and the nurse's role

Many people believe that euthanasia and assisted suicide are condoned carte blanche in the Netherlands. Not true. Both are formally forbidden by criminal law and can be administered only when certain procedures and criteria have been followed. Below, a look at the policies and practices regarding euthanasia and assisted suicide in The Netherlands and the role of nurses in this area.     

Optimization of the weck-Cel collection method for quantitation of cytokines in mucosal secretions

Measurement of immune components in mucosal secretions is important for the evaluation of local immunity at the mucosal surfaces. The Weck-Cel ophthalmic sponge provides a method for the collection of these secretions. The sponge absorbs a relatively large volume of material, therefore allowing for quantitation of multiple immune components. Additionally, it provides a method in which the same device may be used to collect specimens from different mucosal sites, such as the genital tract and oral cavity. This sampling technique has successfully been applied for collection and measurement of antibody in oral and genital tract secretions. The purpose of this work was to optimize the extraction of protein from the sponge matrix. Of particular interest was the recovery of cytokines from the sponge. Satisfactory recovery of the cytokines interleukin 1beta (IL-1beta), IL-2, IL-5, IL-12, IL-6, IL-8, IL-10, and granulocyte-macrophage colony-stimulating factor was obtained. However, IL-4 and gamma interferon recovery rates remained low. Using an alteration of the published extraction method, cytokine concentrations were measured in cervical secretions from women using oral contraceptives. The data revealed detectable concentrations of IL-6, IL-10, IL-8, and IL-12 on cycle days 9 and 20. The proposed technique provides an easy, practical, and consistent method for collection of nonconventional body fluids, such as cervicovaginal fluids and saliva, for the assay of immunoglobulins and several cytokines.     

High rate of coronary artery abnormalities in adolescents and young adults infected with human immunodeficiency virus early in life

We completed a cross-sectional study of individuals infected with human immunodeficiency virus in early childhood using cardiac magnetic resonance imaging and magnetic resonance angiography. Coronary artery abnormality (CAA) was defined by the presence of luminal narrowing and irregularity of the coronary vessel wall. More than 50% of participants (14/27) had evidence of CAA. Individuals had a high rate of CAA, suggesting possible early atherosclerosis.     

Thymic function in HIV infection

Current models hold that CD4+ depletion occurs as a result of direct and indirect effects of HIV, which both kill peripheral CD4+ cells and prevent adequate regeneration. Although age-associated involution diminishes thymic reserve and HIV is clearly thymotoxic, clinical trials have nonetheless shown that large proportions of patients who sustain adequate control of viral replication with highly active antiretroviral therapy (HAART) will demonstrate some evidence for thymic-dependent immune reconstitution, which is associated with improved immune competence. Furthermore, patients with insufficient or absent immune reconstitution following HAART generally lack evidence for thymopoiesis. Current studies are focused on improving our understanding of the causes for thymic failure in HIV infection. Recent work has demonstrated that some HIV strains, especially those that are CXCR4 trophic, are more thymotoxic and may contribute to irreversible thymic damage in this population.     

Brain death and organ donation: an audit in the Irish National Transplantation and Neurosurgical Centre

We set out to identify the reasons why potential organ donors (PODs) fail to become actual donors and the causes of under-utilization of organs offered for donation. We audited 354 patients who died in the intensive Care Unit over 18 months. Of 155 PODs, 78 (50%) did not undergo brain stem testing (BST) because of (i) unavoidable death from non-CNS causes before BST (n = 50), (ii) treatment withdrawal without BST (n = 17) and (iii) preconditions for BST were not fulfilled (n = 11). Brain death was confirmed in 75 patients. Relatives refused consent for donation in 25 patients organ donation was not discussed with the family in 6, and medical contraindications to organ donation prevented donation in 5. Thirty seven (24% of all PODs) became organ donors who provided a total of 216 organ. All donated kidneys were utilized but unsuitability and logistic issues prevented utilization of 20% and 13% of all donated organs respectively. The commonest reason for failure to utilise potential organ donors was failure to perform BST. In most cases this was because BSTs were not possible but more aggressive management of and the routine performance of BST in all PODs could increase the number of donors. Not approaching relatives to ask consent for organ donation and a high rate of refusal by relatives also led to loss of organ donors.     

Thymic function in HIV infection

Current models hold that CD4+ depletion occurs as a result of direct and indirect effects of HIV, which both kill peripheral CD4+ cells and prevent adequate regeneration. Although age-associated involution diminishes thymic reserve and HIV is clearly thymotoxic, clinical trials have nonetheless shown that large proportions of patients who sustain adequate control of viral replication with highly active antiretroviral therapy (HAART) will demonstrate some evidence for thymic-dependent immune reconstitution, which is associated with improved immune competence. Furthermore, patients with insufficient or absent immune reconstitution following HAART generally lack evidence for thymopoiesis. Current studies are focused on improving our understanding of the causes for thymic failure in HIV infection. Recent work has demonstrated that some HIV strains, especially those that are CXCR4 trophic, are more thymotoxic and may contribute to irreversible thymic damage in this population.     

The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features

Microtubule-associated protein tau (MAPT) mutations have been shown to underlie frontotemporal dementia and a variety of additional sporadic tauopathies. We identified a rare p.A152T variant in MAPT exon 7 in two (of eight) patients with clinical presentation of parkinsonism and postmortem finding of neurofibrillary tangle pathology. Two siblings of one patient also carried the p.A152T variant, and both have progressive cognitive impairment. Further screening identified the variant in two other cases: one with pathologically confirmed corticobasal degeneration and another with the diagnosis of Parkinson's disease with dementia. The balance of evidence suggests this variant is associated with disease, but the very varied phenotype of the cases with the mutation is not consistent with it being a fully penetrant pathogenic mutation. Interestingly, this variation results in the creation of a new phosphorylation site that could cause reduced microtubule binding. We suggest that the A152T variant is a risk factor associated with the development of atypical neurodegenerative conditions with abnormal tau accumulation.     

An integrated genetic and functional analysis of the role of type II transmembrane serine proteases (TMPRSSs) in hearing loss

Building on our discovery that mutations in the transmembrane serine protease, TMPRSS3, cause nonsyndromic deafness, we have investigated the contribution of other TMPRSS family members to the auditory function. To identify which of the 16 known TMPRSS genes had a strong likelihood of involvement in hearing function, three types of biological evidence were examined: 1) expression in inner ear tissues; 2) location in a genomic interval that contains a yet unidentified gene for deafness; and 3) evaluation of hearing status of any available Tmprss knockout mouse strains. This analysis demonstrated that, besides TMPRSS3, another TMPRSS gene was essential for hearing and, indeed, mice deficient for Hepsin (Hpn) also known as Tmprss1 exhibited profound hearing loss. In addition, TMPRSS2, TMPRSS5, and CORIN, also named TMPRSS10, showed strong likelihood of involvement based on their inner ear expression and mapping position within deafness loci PKSR7, DFNB24, and DFNB25, respectively. These four TMPRSS genes were then screened for mutations in affected members of the DFNB24 and DFNB25 deafness families, and in a cohort of 362 sporadic deaf cases. This large mutation screen revealed numerous novel sequence variations including three potential pathogenic mutations in the TMPRSS5 gene. The mutant forms of TMPRSS5 showed reduced or absent proteolytic activity. Subsequently, TMPRSS genes with evidence of involvement in deafness were further characterized, and their sites of expression were determined. Tmprss1, 3, and 5 proteins were detected in spiral ganglion neurons. Tmprss3 was also present in the organ of Corti. TMPRSS1 and 3 proteins appeared stably anchored to the endoplasmic reticulum membranes, whereas TMPRSS5 was also detected at the plasma membrane. Collectively, these results provide evidence that TMPRSS1 and TMPRSS3 play and TMPRSS5 may play important and specific roles in hearing.     

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.