UX007 for the treatment of long chain-fatty acid oxidation disorders: Safety and efficacy in children and adults following 24weeks of treatment.

BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) lead to accumulation of high concentrations of potentially toxic fatty acid intermediates. Newborn screening and early intervention have reduced mortality, but most patients continue to experience frequent hospitalizations and significant morbidity despite treatment. The deficient energy state can cause serious liver, muscle, and heart disease, and may be associated with an increased risk of sudden death. Triheptanoin is a medium odd-chain fatty acid. Anaplerotic metabolites of triheptanoin have the potential to replace deficient tricarboxylic acid (TCA) cycle intermediates, resulting in net glucose production as a novel energy source for the treatment of LC-FAOD. STUDY DESIGN: A single-arm, open-label, multicenter Phase 2 safety and efficacy study evaluated patients with severe LC-FAOD evidenced by ongoing related musculoskeletal, cardiac, and/or hepatic events despite treatment. After a four-week run-in on current regimen, investigational triheptanoin (UX007) was titrated to a target dose of 25-35% of total daily caloric intake. Patients were evaluated on several age/condition-eligible endpoints, including submaximal exercise tests to assess muscle function/endurance (12-minute walk test; 12MWT) and exercise tolerance (cycle ergometry), and health related quality of life (HR-QoL). Results through 24weeks of treatment are presented; total study duration is 78weeks. RESULTS: Twenty-nine patients (0.8 to 58years) were enrolled; most qualified based on severe musculoskeletal disease. Twenty-five patients (86%) completed the 24-week treatment period. At Week 18, eligible patients (n=8) demonstrated a 28% increase (LS mean=+181.9 meters; p=0.087) from baseline (673.4meters) in 12MWT distance. At Week 24, eligible patients (n=7) showed a 60% increase in watts generated (LS mean=+409.3W; p=0.149) over baseline (744.6W) for the exercise tolerance test. Improvements in exercise tests were supported by significant improvements from baseline in the adult (n=5) self-reported SF-12v2 physical component summary score (LS mean=+8.9; p<0.001). No difference from baseline was seen in pediatric parent-reported (n=5) scores (SF-10) at Week 24. Eighteen patients (62%) had treatment-related adverse events, predominantly gastrointestinal (55%), mild-to-moderate in severity, similar to that seen with prior treatment with medium chain triglyceride (MCT) oil. One patient experienced a treatment-related serious adverse event of gastroenteritis. One patient discontinued from study due to diarrhea of moderate severity; the majority of patients (25/29; 86%) elected to continue treatment in the extension period. CONCLUSIONS: In patients with severe LC-FAOD, UX007 interim study results demonstrated improved exercise endurance and tolerance, and were associated with positive changes in self-reported HR-QoL.

Deblurring subject to nonnegativity constraints when known functions are present with application to object-constrained computerized tomography.

The reconstruction of tomographic images is often treated as a linear deblurring problem. When a high-density, man-made metal object is present somewhere in the image field, it is a deblurring problem in which the unknown function has a component that is known except for some location and orientation parameters. We first address general linear deblurring problems in which a known function having unknown parameters is present. We then show how the resulting iterative solution can be applied to tomographic imaging in the presence of man-made foreign objects, and we apply the result, in particular, to X-ray computed tomography imaging used in support of brachytherapy treatment of advanced cervical cancer.

The relationship of hardiness and depression to disability in institutionalized older adults.

Disability is an often expensive and sometimes preventable consequence of chronic illness. This study explored the relationship of hardiness and depression to disability in a sample (N = 58) of aged, institutionalized persons, controlling for length of stay (LOS) in the nursing home and physical health status. Using hierarchical regression analysis, LOS and physical health status accounted for 14.7% of the variance in disability (p = .01). Hardiness explained an additional 10.5% of the variance (p = .008). Depression accounted for an additional 7.4% (p = .02) of the variance in disability. The results of this study support the premise that psychological factors may increase a person's degree of disability beyond what might be expected from the physical illness or injury alone.

A systematic review of global cultural variations in knowledge, attitudes and health responses to tuberculosis stigma.

SETTING: Tuberculosis (TB) related stigma is associated with lack of treatment adherence. Individual perceptions of stigma differ by societal context. Limited data are available on variations of TB stigma worldwide. OBJECTIVE: To describe the influence of TB stigma on knowledge, attitudes and responses to TB and to identify similarities and differences across countries. DESIGN: Systematic review of international descriptive studies. RESULTS: A total of 1268 studies were identified from PubMed/Medline, Web of Science, Cochrane, PsycINFO and Cumulative Index to Nursing and Allied Health Literature database searches. Eighty-three studies from 35 countries met the inclusion criteria for English, peer-reviewed, original and non-interventional studies. Variation and similarities in the influence of TB stigma on knowledge, attitudes and responses to TB across countries were identified. Stigma antecedents included negative attitudes and misperceptions regarding the causes of TB and the association with the human immunodeficiency virus. Decisions about illness disclosure and choices between traditional healers and public or private providers were influenced by TB stigma. Sex-influenced perceptions and management of TB and public health responses contributed to TB stigma. CONCLUSION: Our findings confirm cultural variations with respect to TB and the potential for stigma. Cultural variations should be considered in the development of interventions aimed at reducing stigma and improving treatment adherence.

The use of compression stockings for venous disorders in Brazil.

OBJECTIVE: The aim of this study was to analyse the medical indication and the use of elastic compression stockings, and to assess patient adherence to treatment in different regions of Brazil. METHOD: The prescription and clinical indication of elastic stockings were evaluated in a prospective, descriptive, cross-sectional, multicentre study for a population of private patients. In 2009, 3414 patients from 123 treatment centres in southern, south-eastern and north-eastern Brazil were evaluated using a questionnaire. The following variables were analysed: sociodemographic (gender, age, occupation and education), lifestyle (physical activity and time spent standing); classification of venous disease (CEAP [clinical, aetiological, anatomical and pathophysiological] classification--clinical criteria), indications for prescription, consumer behaviour (strength, acquisition and use of stockings) and criteria of satisfaction (improvement, duration of use, adherence). The effects of compression therapy were assessed at a follow-up visit approximately 30 days after starting treatment with the following items being assessed: complaints about pain, discomfort, burning sensation and oedema of the leg while using elastic stockings. Multivariate analysis was used to compare data with an alpha error of 5% (P value < 0.05) being considered acceptable. RESULTS: The average age increased with the severity of chronic venous insufficiency; the main indications used by physicians were leg pain and discomfort; 89.3% of patients bought stockings and thus started treatment with more than 90% of these reporting improvements in symptoms. CONCLUSION: Elastic stockings are available to the Brazilian population, look acceptable at the time of purchase and provide good results; however, some limitations regarding their use need to be addressed.

Hardiness and death attitudes: predictors of depression in the institutionalized elderly.

There are varied and high estimated prevalence rates of depression in the institutionalized elderly. Personality characteristics and attitudes are two attributes in the uniqueness of humans that have been overlooked in explaining depression. This study examined the relationships of hardiness and death attitudes to depression. The sample consisted of 90 consenting participants; 46 women and 44 men. The mean age of the sample was 73.3 years. This study produced the following three major findings: hardiness and depression are correlated; healthy death attitudes are related to low depression scores; and the combination of nonhardiness and health-limiting death attitudes are reliable predictors of depression in the institutionalized elderly.

The role of advanced practice psychiatric nurses in treating tobacco use and dependence.

Tobacco use is treatable and the benefits of smoking cessation are impressive, yet like other health care providers, psychiatric nurses have failed to consistently assess and treat tobacco use effectively. Tobacco use continues to cause illness, disability, and death at unprecedented rates. Nicotine addiction is drug abuse and it is a chronic disease and needs to be treated as such. There are clear health benefits to smoking cessation regardless of the age of smoking initiation or the age of smoking cessation. Advanced practice psychiatric nurses (APPNs) are in a unique position to make an impact on a smoker's risk of suffering from tobacco-related diseases: the treatment of choice is the combination of pharmacotherapy and psychosocial interventions, both within the realm of APPN practice; psychiatric and substance abusing patients consistently demonstrate increased rates of cigarette smoking compared with healthy controls; and tobacco use is drug abuse, a treatable chronic disease. The ability of APPNs to deliver psychotherapeutic and pharmacologic care secures a position in the forefront of treating tobacco use. In addition to intervention, psychiatric nurses need to step up and take an active role in initiating and supporting tobacco control policy and legislation.

Motivation of voluntary plasmapheresis donors.

A totally voluntary plasmapheresis program recruits 900 individual donors per year at a cancer institute, where 500 to 900 units of platelets are transfused each month. Staff and donors use a film and brochures to recruit donors from the local community. Television and radio spots, with donor recognition pins, certificates, receptions, and picnics are utilized. Donor motivation was studied by use of: 1) California Psychological Inventory--measures a variety of "normal" personality traits; 2) Study of values--measures theoretical, economic, aesthetic, social, political, religious values; 3) Internal-External Control Scale--measures degree to which a person blames self vs. external events for what happens to him; 4) Faith in People Scale--measures individual's confidence in his fellow man; 5) Anomia Scale--measure of feelings of self-to-others alienation; 6) Mach IV Scale--measure of persons tendency to manipulate others; and 7) Biographical Data Form. Results are presented for 25 male donor subjects studied, as they compare with normative data for the scales used. Donors appeared to have the same traits as do the general population, but appeared lower in Machiavellianism than non-plasmapheresis donors. Prospective study plans include additional subjects to provide appropriate control groups.

Perceived latitude of choice of institutionalized and noninstitutionalized elderly women.

An Importance, Locus and Range of Activities Checklist, designed to assess self-perceived latitude of choice, a self concept and a life satisfaction scale were administered to 25 institutionalized and 25 noninstitutionalized elderly females. The checklist contained statements about 37 activities of daily living which subjects rated for personal importance and degree of choice available to them. The derived latitude of choice score was based jointly on importance and choice ratings for each activity. Institutionalized respondents, living in a relatively restrictive environment, earned significantly lower latitude of choice scores than did noninstitutionalized subjects. Latitude of choice, self concept and life satisfaction scores were significantly correlated. These findings attest to the appropriateness of the technique used to assess perceived latitude of choice. Modifications of the Importance, Locus and Range of Activities Checklist designed to provide a more profound measure of latitude of choice and to improve the applicability of the scale to different categories of respondents were discussed.

Life-span differences in life satisfaction, self-concept, and locus of control.

The literature on age differences in life satisfaction, self-concept, and locus of control reveals a variety of conflicting findings. Nehrke et al. reported a study of elderly institutionalized males that attempted to control for some of the possible sources of variability. The present study extended this effort to a noninstitutionalized life-span sample of males and females in six age groups (fourteen to ninety-four). The age main effect was significant for the locus of control measure. For self-concept, the age and sex main effects were significant. For life satisfaction, the age and sex main effects and their interaction were significant. Generally, lower levels of self-concept and life satisfaction and a more external orientation characterized adolescents and young adults while, with notable exceptions, the remaining age samples were more positive in self-concept and life satisfaction and were more internally controlled. Although the three dependent measures were significantly correlated for the total sample, the correlations involving locus of control were only moderate. The data suggest that at least the life satisfaction and self-concept measures may be viable tools to assess the psychological quality of one's life, and that reliable age differences in well-being can be demonstrated if moderating variables are controlled experimentally or statistically.

Murine monoclonal anti-DNA antibodies bind directly to glomerular antigens and form immune deposits.

The capacity of monoclonal anti-DNA antibodies, derived spontaneously from MRL-lpr/lpr mice, to bind directly to intrinsic glomerular antigens and form immune deposits was evaluated. Two antibodies, H130 (IgM-kappa) and H241 (IgG2a-kappa), bound to normal glomeruli in vitro. This binding was not inhibited by DNAase, but it was, in the case of H130, inhibited by the anti-idiotype anti-H130. Both antibodies also bound to glomerular digests on nitrocellulose. After i.v. injection, however, H241 bound to glomeruli and formed glomerular immune deposits, whereas H130 did not. Similarly, after i.p. injection of H241 hybridomas to normal mice, all mice developed glomerular immune deposits. In contrast, administration of H130 hybridomas, other anti-DNA-producing hybridomas, and other unrelated hybridomas did not lead to glomerular immune deposit formation. We conclude that certain lupus auto-antibodies can form glomerular immune deposits by binding directly to non-DNA antigenic structures that are normally present in extracellular locations within normal glomeruli.

Role diversification in the education of advanced practice psychiatric nurses.

The mode, location, and focus of health care services are changing rapidly, especially delivery of psychiatric services. The high prevalence of psychiatric and medical comorbidity, the national shift in health care to a managed care arrangement with one professional designated as principle provider, and problems with access to comprehensive services for individuals with psychiatric problems interact to create a compelling need for a clear definition of advanced psychiatric-mental health nursing practice. This article is, in part, a response to the national dialogue and debate sparked by the beginning development of a psychiatric nurse practitioner certification exam. However, this debate will be used merely as a starting point to articulate and document the need for a flexible, diverse, and evolving definition of advanced psychiatric-mental health nursing practice that can inform and shape educational programs in the discipline.

A comparison of the pharmacological properties of carbohydrate remodeled recombinant and placental-derived beta-glucocerebrosidase: implications for clinical efficacy in treatment of Gaucher disease.

The objective of these studies was to characterize the macrophage mannose receptor binding and pharmacological properties of carbohydrate remodeled human placental-derived and recombinant beta-glucocerebrosidase (pGCR and rGCR, respectively). These are similar but not identical molecules that were developed as enzyme replacement therapies for Gaucher disease. Both undergo oligosaccharide remodeling during purification to expose terminal mannose sugar residues. Competitive binding data indicated carbohydrate remodeling improved targeting to mannose receptors over native enzyme by two orders of magnitude. Mannose receptor dissociation constants (Kd) for pGCR and rGCR were each 13 nmol/L. At 37 degrees C, 95% of the total macrophage binding was mannose receptor specific. In vivo, pGCR and rGCR were cleared from circulation by a saturable pathway. The serum half-life (t1/2) was 3 minutes when less than saturable amounts were injected intravenously (IV) into mice. Twenty minutes postdose, beta-glucocerebrosidase activity increased over endogenous levels in all tissues examined. Fifty percent of the injected activity was recovered. Ninety-five percent of recovered activity was in the liver. Parenchymal cells (PC), Kupffer cells (KC), and liver endothelium cells (LEC) were responsible for 75%, 22%, and 3%, respectively, of the hepatocellular uptake of rGCR and for 76%, 11%, and 12%, respectively, of the hepatocellular uptake of pGCR. Both molecules had poor stability in LEC and relatively long terminal half-lives in PC (t1/2 = 2 days) and KC (t1/2 = 3 days).

Estenosis anal por granuloma inguinal / Anal stenosis by granuloma inguinale

Se presenta un caso de granuloma inguinal, afección poco frecuente en nuestro medio. La forma clínica correspondió a la ubicación perigenital con estenosis anal y cuadro suboclusivo. Esta se observa con mayor frecuencia en los homosexuales, presentándose con características propias que se detallan. La lesión estenótica en estos casos es de hallazgo excepcional

Estenosis anal por granuloma inguinal / Anal stenosis by granuloma inguinale

Se presenta un caso de granuloma inguinal, afección poco frecuente en nuestro medio. La forma clínica correspondió a la ubicación perigenital con estenosis anal y cuadro suboclusivo. Esta se observa con mayor frecuencia en los homosexuales, presentándose con características propias que se detallan. La lesión estenótica en estos casos es de hallazgo excepcional (AU)

Efectos de los corticoides en anastomosis colonicas en ratas. / Effects of corticoids in colonic anastomosis in rats

Se estudio en forma prospectiva, randomizada y doble ciego una serie de 40 ratas Wistar, analizando el efecto de los glucocorticoides en anastomosis colonicas. Se observo una diferencia estadisticamente significativa, entre ambos grupos, visualizandose que las tratadas con dexametasona presentaban mayores complicaciones, especialmente dehiscencias parciales o totales de las anastomosis. Se describe el mecanismo de accion de los glucocorticoides y se discute su probable influencia en los resultados obtenidos