Self‐Neglect: A Proposed New NANDA Diagnosis

PURPOSE. To propose a new NANDA diagnosis, self‐neglect. DATA SOURCES. Research studies and literature published from a variety of disciplines including nursing as well as primary research. DATA SYNTHESES. This diagnosis can be used to describe a constellation of self‐care problems of varying severity and impact on the health and well‐being of people who self‐neglect. Included are two subtypes of self‐neglect based on the degree of intentionality. Clarification of self‐neglect is long overdue because self‐neglect presents conceptual, identification, and intervention problems for nurses, healthcare workers, and for medicolegal systems across settings and in many countries. CONCLUSION. The proposed diagnosis, self‐neglect, fills a gap in current standardized terminology. This diagnosis will contribute significantly to nurses leading the way in the explication of an interdisciplinary and international health concern. PRACTICE AND POLICY IMPLICATIONS. Developing self‐neglect as a recognized nursing label is vital to clinicians and policy makers within and across countries. Appreciating less serious/non‐life‐threatening presentations will give nurses a care perspective to improve the health and well‐being of those in earlier stages of self‐neglect. Definitions for this phenomenon will contribute to care planning and interventions, leading to consistency in practice and research.     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².     

Time-dependent morphological alterations of cold-stored small bowel in Euro-Collins and Ringer's lactate solutions

Small bowel is one of the organs that can in principle be transplanted. Optimum preservation of the organ is essential for the success of transplantation. The aim of the present study is the investigation of time-related morphological changes of rat small bowel during preservation in hypothermic Euro-Collins (EC) and Ringer's lactate (RL) solution using light microscopy and transmission electron microscopy to evaluate the integrity of intercellular complexes of mucosal epithelium, one of the tissues of the intestine that is most susceptible to ischemia. Small bowels were perfused with either EC, RL solution or physiological saline solution and were placed in the different preservation solutions at 4 degrees C for 0, 3, 6 and 12 h. The results of our study suggest that both preservation solutions are suitable for short-term preservation of the small bowel although RL solution is more effective than EC solution. However, we conclude that further improvement of preservation solutions and/or techniques are needed to perform long-term preservation.     

Regulatory effects of biophysical strain on rat TMJ discs

Recent studies have revealed that dynamic biomechanical forces can exert antiinflammatory and antiproteolytic effects on fibrocartitage. Whether the effects of mechanical strain also involve stimulation of the insulin-like growth factor (IGF) system and, therefore, of growth and repair of fibrocartilage has yet to be determined. The objective of this in vitro study was to determine if continuous biophysical strain regulates the gene expression of IGF1, IGF2, IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), and IGF-binding proteins (IGFBP) 3 and 5 in cells from the fibrocartilaginous disc of the temporomandibular joint (TMJ). Rat TMJ disc cells were subjected to continuous biophysical strain (3% and 20%) for 4 and 24 h. Subsequently, RNA was extracted and real-time PCR was performed using an iCycler iQ detection system to analyze the gene expression of the IGF system. The gene expression of IGF1, IGF2, IGF1R, IRS1, IGFBP3, and IGFBP5 was significantly (p < 0.05) inhibited when cells were subjected to continuous biophysical strain, as compared to control at both time points. High strain induced a stronger inhibition of these molecules as compared to strain of Low magnitude. In conclusion, continuous biophysical strain seems to downregulate the expression of the IGF system and may, therefore, reduce the potential of fibrocartilage for growth and repair.     

Construction and characterization of Listeria monocytogenes mutants with in-frame deletions in the response regulator genes identified in the genome sequence

Two-component systems are widely distributed in prokaryotes where they control gene expression in response to diverse stimuli. To study the role of the sixteen putative two-component systems of Listeria monocytogenes systematically, in frame deletions were introduced into 15 out of the 16 response regulator genes and the resulting mutants were characterized. With one exception the deletion of the individual response regulator genes has only minor effects on in vitro and in vivo growth of the bacteria. The mutant carrying a deletion in the ortholog of the Bacillus subtilis response regulator gene degU showed a clearly reduced virulence in mice, indicating that DegU is involved in the regulation of virulence-associated genes.     

Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study

BACKGROUND: Increased total serum IgE levels are a common characteristic of atopic disorders. Six potentially functional variants, including C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene, have been evaluated for their involvement in the control of total serum IgE levels and related atopic disorders, but the results of these studies have been inconsistent. OBJECTIVE: We examined whether these 6 variants had genotypic effects on total serum IgE levels in 823 unrelated German children from a large infant cohort, the German Multicenter Atopy Study. METHODS: Marginal effect models were used for the analyses of the repeated IgE measurements. Weighted linear regression and family-based tests of association were performed to minimize the possibility of spurious effects caused by selection bias or confounding on the basis of ethnic background. RESULTS: There are significant associations between increased total serum IgE levels and 2 variants in the IL13 gene (P <.005 and.0002 for Arg130Gln and C-1055T, respectively). These genetic effects are unlikely to be due to solely linkage disequilibrium between 2 polymorphisms, population stratification, or nonrepresentative samples. In addition, exposure to maternal smoking appears to modify the above effects on total serum IgE levels. However, no statistical association was observed between this quantitative phenotype and the other 4 variants examined. CONCLUSION: These findings suggest that variants C-1055T and Arg130Gln of the IL13 gene might play an important role on total serum IgE production in this study population.     

Lipopolysaccharide contamination of beta-lactoglobulin affects the immune response against intraperitoneally and orally administered antigen

BACKGROUND: Microbial components in the environment are potent activators of the immune system with capacity to shift the active immune response towards priming of Th1 and/or Th2 cells. Lipopolysaccharide (LPS), a cell-wall component of Gram-negative bacteria, is extensively present in food products like cow's milk. It is not well established, however, how this presence of LPS affects oral tolerance induction. METHODS: We studied the effect of LPS contamination in a commercial preparation of the cow milk protein beta-lactoglobulin (beta-LG) on antigen-specific immune responses. IgG1/IgG2a production upon intraperitoneal immunization without adjuvant was measured, and oral tolerance induction against beta-LG after administration of either an aqueous solution or water-in-oil (w/o) emulsion of beta-LG was evaluated. RESULTS: LPS contamination of beta-LG provoked a beta-LG-specific IgG2a response, as well as an enhanced beta-LG-specific IgG1 response upon intraperitoneal immunization. Oral tolerance induction to beta-LG was induced by aqueous solutions of beta-LG with and without LPS administration. Conversely, oral administration of w/o-emulsified beta-LG prevented oral tolerance to beta-LG only when the beta-LG was contaminated with LPS. CONCLUSIONS: LPS contamination of an aqueous protein solution does not affect oral tolerance induction, whereas LPS present in emulsion prevents oral tolerance induction towards the food protein.