Lack of apoptosis in patients with progressive external ophthalmoplegia and mutated adenine nucleotide translocator-1 gene

Adenine nucleotide translocator-1 (ANT-1), encoded by chromosome 4 (4q34-35 locus), is a component of the mitochondrial permeability transition pores that are involved in apoptotic mechanisms. We studied muscle biopsies from seven individuals with autosomal dominant progressive external ophthalmoplegia caused by ANT-1 mutations. We found no instance of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) positivity nor significant expression of apoptosis-related proteins. Furthermore, there was no morphological evidence of apoptosis at the ultrastructural level. Thus, degeneration of muscle in this disorder is nonapoptotic.     

IgG-immunostaining in the intact rabbit brain: variable but significant staining of hippocampal and cerebellar neurons with anti-IgG

A significant number of brain neurons in the rabbit brain were immunostained with anti-rabbit gamma-immunoglobulin (IgG). IgG-positive neurons were often found in the cerebellum, lower brainstem and motor nuclei. Similar IgG-positive neurons were occasionally found in the hippocampus, cerebral cortex and midbrain, but not in the striatum and thalamus. These neurons showed very clear Golgi-like staining of soma and dendrites but IgG staining was absent from the cell nuclei and axons. In particular, groups of Purkinje neurons in the rabbit cerebellum showed strong IgG-positive staining. To confirm whether the staining reflected the existence of IgG molecules in these neurons, staining specificity was carefully evaluated. Staining was specifically eliminated by pre-absorption of the antibodies with the purified rabbit IgG. An antibody to the neural cell adhesion molecule (NCAM or CD56), a member of the immunoglobulin superfamily, exhibited a completely different pattern of staining as that for IgG. To determine whether IgG-like immunoreactivity was a general feature of mammalian brain, brain sections of rabbits, rats, and mice were immunostained with antibodies to IgGs of each of the three species. Similar IgG-positive neurons were observed in all three species, although the distribution and frequency was characteristic for each species. In rabbit brain, anti-rabbit IgG stained-neurons were more abundant compared to rat and mouse brain. IgG-positive microglia-like cells were evident in mouse brain, but less frequent in rabbit and were hardly observed in rat brain. To evaluate whether stained neurons could synthesize IgG, in situ hybridization was carried out using an antisense oligonucleotide probe to rabbit IgG DNA. No significant label was observed in cerebellum. These results suggest that a significant number of neurons in the intact rabbit brain take up IgGs and concentrate them in their cytoplasm, although the molecular uptake mechanism is retained for future studies. Our results also suggest that the rabbit may be a suitable animal to study the function(s) of IgG in brain neurons.     

Research within the field of blood and marrow transplantation nursing: how can it contribute to higher quality of care?

Nursing Science and research within BMT started in the early 80s and has been shown to be a useful contribution to obtain and maintain high standards of care. Trial and error are no longer accepted. The first studies were conducted together with the clinical developments and focused specifically on symptom control and management of the treatment. The term "evidence-based nursing" (EBN) is nowadays often used to describe the influence of research on practice. And yet we find that in general, care given by nurses is not yet based according to the guidelines established by research. There are several reasons why care is not (yet) based on results from research, like language barrier, diversity in health care and nursing educational systems, financial restrains and different roles and perceptions of nurses around the globe. Many nursing or multidisciplinary research studies have been conducted worldwide on areas such as the prevention or care for patients with mucositis, fatigue or pain, care for the central venous access devices, outpatient management of care, care for the donor and aspects of quality of life. Results have implications on practice and start to show their impact on quality of care. Many questions remain unanswered. Results from basic science (e.g. the discussion around fetal liver and embryonic derived stemcells and their use in treatment other than hematologic malignancies) and developments in medical treatments (e.g. introduction of tyrosin-kinase inhibitor, biotherapy and genetherapy) have an impact on nursing and should therefore be investigated closely to develop clinical pathways. It is obvious that much more time, finances, collaboration and support is needed to conduct powerful studies that can influence care for the BMT patient. This presentation will focus on developments through nursing research within the field of BMT and discuss gaps that will need to be filled in the near future.     

Effects of hematocrit changes on flow-mediated and metabolic vasodilation in humans

Endothelial function is noninvasively assessed by measuring nitric oxide-dependent increase in radial artery diameter accompanying the elevation in shear stress induced by increasing blood flow through a short-lasting ischemia of the hand. However, shear stress also depends on blood viscosity, whose changes might thus affect nitric oxide increase in a manner that is not properly reflected by blood flow changes. In 12 subjects with hemochromatosis, we measured ultrasonographically radial artery diameter and blood flow responses to a 4-minute ischemia of the hand. This was done also after removing 500 mL of blood (and concomitantly infusing 500 mL of saline), which significantly (P<0.01) reduced hemoglobin concentration and hematocrit. The increase in blood flow induced by the 4-minute ischemia was similar before and after blood removal (+76% and +80%), which, in contrast, markedly attenuated the accompanying increase in radial artery diameter (+25% versus +13%, P<0.01). Thus, in humans, blood viscosity is involved in the endothelial response to an increase in shear stress. This implies that this response may not be accurately assessed and compared by quantifying the stimulus only through an increase in blood flow.     

Prevalence of hepatitis C in U.S. Army aircrew: do flaws in the data exist?

BACKGROUND: Hepatitis C virus (HCV) infection is a rare condition with unknown prevalence in Army aircrew. This is a retrospective serial prevalence study to determine the prevalence of HCV in Army aircrew and discuss whether this reflects the true prevalence rate. METHOD: The Aviation Epidemiology Data Registry (AEDR) at the U.S. Army Aeromedical Center was queried by ICD-9-CM codes for cases of hepatitis from January 1988 to October 1999. These records were further reviewed for documented cases of HCV. Case details were extracted and then the data were evaluated. RESULTS: The prevalence rate in this population is exceedingly low at 0.000087 cases per year averaged over the 12 yr, or 1 case in 11,000 aircrew per year with an average of 24,077 records per year. The total number of cases was 31, with 22 of those involving pilots. Subjects averaged 15.26 yr of military service. CONCLUSION: The prevalence of HCV in aircrew is low and is much lower than in the general and military populations. These prevalence rates may be skewed low due to lack of universal reporting method, no screening, and asymptomatic nature of initial infection. Conversely, the prevalence may be accurate due to high fitness levels, population motivation, and required healthcare visits. Current prevalence rates do not support a need for universal screening, but the cost of case detection in lost training dollars and experience is significant. A definitive study would assess the true prevalence rate and determine if screening in this population is warranted.     

The Georgia Emerging Infections Program: monitoring trends in invasive pneumococcal disease

The active, population-based surveillance system of the Georgia EIP has provided valuable insights into the characteristics of invasive pneumococcal disease in Georgia and continues to provide an important mechanism to assess the impact of the newly introduced PCV7 vaccine. The problem of antimicrobial resistance has been carefully documented among isolates from invasive pneumococcal disease in all age groups, particularly young children. Fluoroquinolone resistance is now present in our area and will require close monitoring in the coming months and years. Over 80% of invasive pneumococcal disease and over 85% of penicillin and cefotaxime resistant invasive disease occurring in young children in our surveillance area involve serotypes included in the new conjugate vaccine approved for use in children. Preliminary data suggest an early decline in invasive pneumococcal disease in young children has occurred since the introduction of the conjugate vaccine and the effect upon the prevalence of antimicrobial resistance remains to be determined. The high rates of invasive pneumococcal disease, the significant associated morbidity and mortality and antimicrobial resistance highlight the need for enhanced prevention measures in both adults and children. Ongoing surveillance in the Georgia EIP will allow accurate measurement of the impact of prevention efforts, provide essential information on trends in antimicrobial resistance and document any changes in the pneumococcal serotypes responsible for invasive disease in the conjugate vaccine era.     

The diagnosis and treatment of childhood melanoma

The incidence of melanoma in prepubertal children is 0.3% to 0.4%, with 2 percent of all melanomas occurring in patients under the age of 20 years. Superficial spreading and nodular melanomas are the most common subtypes in childhood melanoma. This article describes conditions associated with an increased incidence of juvenile melanoma and how to best manage this disease.