Boundary Ambiguity in Parents With Chronically Ill Children: Integrating Theory and Research

Abstract: This article integrates theory and research related to boundary ambiguity in parents of children with a chronic health condition. We propose that boundary ambiguity is a risk factor for psychological distress in these parents. Clinical applications and a case example highlight how boundary ambiguity can be assessed and managed in clinical settings by professionals working with parents with chronically ill children. Questions are provided for assessing boundary ambiguity in clinical and research settings, and implications for research are discussed.     

Technology anxiety as a potential mediating factor in response to medical technology

Technology anxiety, defined as a fear of working with medical equipment, was measured via the use of the Technology Response Questionnaire. Nurses (N=414) working on nine types of nursing units at two hospitals participated in the study. Nurses working on psychiatric units were found to be most anxious about working with medical equipment, while nurses working on surgical and adult intensive care units were least anxious. A comparison of the nurses who were highest and lowest on technology anxiety indicated that those who were most anxious about technology were less positive toward computers, felt more stressed by their work, were lower on job satisfaction, less positive toward the physicians they worked with, lower on personality scales of autonomy and adaptability, were less likely to do care planning regularly or to use nursing diagnoses, and tended to be older than less anxious nurses.     

Do discrepancies in interpersonal perception predict relapse?: A comparison of remitted depressed patients and collaterals

In an effort to examine whether disturbed interpersonal relationships are associated with relapse in depression, discrepancies in self-ratings provided by formerly depressed patients and their collateral informants were compared. Thirty-eight remitted depressed patients and their collateral informants were asked to monitor moods, life events, and stress levels on a bimonthly basis for a 1-year period. It was hypothesized that patient/collateral dyads displaying a greater discrepancy in interpersonal perception would have a higher risk of relapse than dyads who showed more agreement in their ratings. Results indicated that while discrepancies in the perceptions of patients' life events were associated with the duration of a relapse once it occurred, discrepancies were generally not related to the emergence of new episodes of depressive disorder. The implications of these findings for models seeking to integrate cognitive and interpersonal models of depression, through the study of environmentally determined and personally appraised adversity, is discussed.This research was supported by grants to the first and third authors from the Canadian Psychiatric Research Foundation and the Laidlaw Foundation.     

Prednisone-Free Maintenance Immunosuppression—A 5-Year Experience

Concern persists that prednisone-free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5-year follow-up of a trial of prednisone-free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death-censored graft survival, 92%; acute rejection-free graft survival, 84% and chronic rejection-free graft survival, 87%. The mean serum creatinine level (+/-SD) at 1 year was 1.6 +/- 0.6; at 5 years, 1.7 +/- 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone-free as of April 30, 2005. As compared with historical controls, recipients on prednisone-free maintenance immunosuppression had a significantly lower rate of a number of complications, including cataracts (p < 0.001), posttransplant diabetes mellitus (p < 0.001), avascular necrosis (p = 0.001), and fractures (p = 0.004). We conclude that prednisone-related side effects can be minimized in a protocol incorporating prednisone-free maintenance immunosuppression. Five-year graft outcome remains good.     

Kathepsin D bei Ovarialtumoren

Zusammenfassung In der vorgestellten Arbeit wurden insgesant 15 Ovarialtumoren auf ihren Kathepsin D-Gehalt untersucht. Sowohl bei den benignen Ver?nderungen wie auch bei den malignen konnte diese Protease nachgewiesen werden. Bei den malignen Tumoren fand sich keinerlei Korrelation des Kathapsin D zur Exprimierung des Markers Ca 125 und zum ?strogenrezeptorbesatz.     

Local tissue properties in bone healing: Influence of size and stability of the osteotomy gap

To characterize the site-specific mechanical and histological properties in fracture repair and to relate these properties to the initial mechanical situation, an experimental fracture model was used in the metatarsus of 42 sheep. the mechanical situation of a transverse osteotomy was described by three gap sizes (1,2, or 6 mm) and two amounts of strain (7 or 31 %). An external fixator that allowed a defined axial movement provided control of these settings. Nine weeks following surgery, the healing area was dissected and tensile and compressive properties were measured in subregions of the fracture gap and the periosteal callus. The central, sagittal section was used for quantitative histology. We found the quality of the tissue along the osteotomy line to be most important for regaining mechanical stability. Increasing the size of osteotomy gaps resulted in poorer mechanical and histological qualities, and the repair process was less complete. Interfragmentary strain did not significantly influence the repair process. The smaller strain levels had already stimulated the secondary repair process, and this stimulatory effect could not be further enhanced by increasing the amount of strain. Our finding that large gaps between bone segments were not as well healed as were smaller gaps suggests that it is advantageous to avoid large gaps in fracture treatment.     

Individual differences in adult human sleep and wakefulness: Leitmotif for a research agenda

This paper reviews the literature on interindividual variability in human sleep parameters, sleepiness, responses to sleep deprivation, and manifestations of sleep disorders. Variability among individuals in sleep/wake biology and behavior is pervasive. The magnitude of such individual differences is often considerable and comparable to the effect sizes of many experimental and clinical interventions. Evidence is accumulating that certain aspects of sleep/wake-related variability--such as sleep duration, daytime sleepiness, and vulnerability to the effects of sleep loss--involve trait characteristics in healthy populations and among sleep-disordered patients. Establishing the trait-specific nature of variability in sleep/wake parameters is a prerequisite for elucidating the corresponding neurophysiologic and/or genetic mechanisms. At present, it remains largely unknown what underlies or predicts sleep/wake-related traits, what relationships these traits may have to each other, and what functional significance may be associated with specific traits. Scientific studies addressing these issues are warranted, as understanding the basis of trait variability may yield new insights into sleep/wake regulation and sleep pathology. Understanding individual differences in sleep and wakefulness may also have provocative but important implications for health economics and clinical care, as well as for safety, productivity, and general well-being. This paper gives suggestions for a research agenda focusing on individual differences in sleep research and sleep medicine.     

Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85alpha

The signaling enzyme phosphoinositide 3-kinase (PI3K) is activated following B cell receptor (BCR) engagement and by many other receptors on B lymphocytes. Mice lacking p85alpha, the predominant PI3K regulatory isoform, exhibit defects in B cell development and activation that are grossly similar to those found in mice lacking Bruton's tyrosine kinase (Btk) and other critical signaling molecules. However, a detailed analysis of splenic B cell subsets in p85alpha-deficient mice has not been reported. Here we show that these mice are deficient in four major B cell subsets: transitional-1, transitional-2, follicular and marginal zone. These defects are distinct from those observed in Xid mice that express a mutant Btk unable to interact with PI3K lipid products. Moreover, mice with both genetic lesions exhibit even greater impairment in B cell development. Finally, we show that transgenic expression of the anti-apoptotic protein Bcl-2 in p85alpha-deficient mice restores the transitional B cell subsets but not the marginal zone subset, and produces a follicular population with an aberrant phenotype. These findings establish a role for PI3K-p85alpha in differentiation of both follicular and marginal zone B cells, and suggest that these functions are required not solely for the propagation of anti-apoptotic signals.     

Cognitive Function and Quality of Life in Vorinostat-Treated Patients after Matched Unrelated Donor Myeloablative Conditioning Hematopoietic Cell Transplantation

Myeloablative conditioning allogeneic hematopoietic cell transplantation (HCT) puts patients at greater risk for significant cognitive and quality of life decline compared with recipients of reduced-intensity conditioning or autologous HCT. Vorinostat, a histone deacetylase inhibitor, has been shown to have neuroprotective and neurorestorative effects in preclinical models of neurologic diseases. Thus, within the context of a myeloablative conditioning phase II clinical trial of vorinostat combined with tacrolimus and methotrexate for graft-versus-host disease prophylaxis, we conducted an ancillary study to evaluate feasibility of assessing associations between vorinostat and neurocognitive function and quality of life (ClinicalTrials.gov NCT02409134). Nine patients (mean age, 53 years; range, 36 to 66) underwent computerized neuropsychological testing (Cogstate) and completed surveys of mood (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), and quality of life (Functional Assessment of Cancer Therapy–General). Control cohorts from a separate concurrent longitudinal study (19 autologous and 18 allogeneic HCT patients, who matched the vorinostat patients on relevant medical and demographic variables) completed the same test battery. All allogeneic patients received busulfan-based myeloablative conditioning and were transplanted with HLA-matched unrelated donors. The total neurocognitive performance score of vorinostat patients did not change significantly across the study duration (ie, baseline, day 30, day 100, and day 160). Depression, anxiety, and quality of life also did not differ significantly across time. In univariate analyses (analysis of variance), vorinostat-treated patients showed no difference in neurocognitive function or quality of life compared with autologous and allogeneic control subjects. However, when medical variables were accounted for in a linear mixed effects regression model, the total neurocognitive performance of vorinostat-treated patients was comparable with autologous control subjects. Notably, autologous control subjects performed significantly better than allogeneic control subjects (estimate, .64; standard error, .23; P ≤ .01). Moreover, a smaller percentage of vorinostat-treated patients were classified as mildly, moderately, or severely impaired across neurocognitive domains as well as time points compared with both control cohorts. Thus, vorinostat may have neurorestorative or neuroprotective effects in the HCT setting. Accordingly, we recognize the need for a future, full-scale randomized controlled trial to further examine this hypothesis.     

Survival and Implantation of Escherichia coli in the Intestinal Tract

Preliminary experiments established that a 0.5-ml inoculum that is introduced directly into the stomach of mice was cleared rapidly into the small intestine. Bicarbonate buffer, but not skim milk, protected such an inoculum from stomach acid until at least 90% of it had entered the small intestine. Passage and survival of various Escherichia coli strains through the mouse gut were tested by introducing a buffered bacterial inoculum directly into the stomach, together with the following two intestinal tracers: Cr(51)Cl(3) and spores of a thermophilic Bacillus sp. Quantitative recovery of excreted bacteria was accomplished by collecting the feces overnight in a refrigerated cage pan. The data show that wild-type E. coli strains and E. coli K-12 are excreted rapidly (98 to 100% within 18 h) in the feces without overall multiplication or death. E. coli varkappa1776 and DP50supF, i.e., strains certified for recombinant DNA experiments underwent rapid death in vivo, such that their excretion in the feces was reduced to approximately 1.1 and 4.7% of the inoculum, respectively. The acidity of the stomach had little bactericidal effect on the E. coli K-12 strain tested, but significantly reduced the survival of more acidsensitive bacteria (Vibrio cholerae) under these conditions. Long-term implantation of E. coli strains into continuous-flow cultures of mouse cecal flora or into conventional mice was difficult to accomplish. In contrast, when the E. coli strain was first inoculated into sterile continuous-flow cultures or into germfree mice, which were subsequently associated with conventional mouse cecal flora, the E. coli strains persisted in a large proportion of the animals at levels resembling E. coli populations in conventional mice. Metabolic adaptation contributed only partially to the success of an E. coli inoculum that was introduced first. A mathematical model is described which explains this phenomenon on the basis of competition for adhesion sites in which an advantage accrues to the bacterium which occupies those sites first. The mathematical model predicts that two or more bacterial strains that compete in the gut for the same limiting nutrient can coexist, if the metabolically less efficient strains have specific adhesion sites available. The specific rate constant of E. coli growth in monoassociated gnotobiotic mice was 2.0 h(-1), whereas the excretion rate in conventional animals was -0.23 h(-1). Consequently, limitation of growth must be regarded as the primary mechanism controlling bacterial populations in the large intestine. The beginnings of a general hypothesis of the ecology of the large intestine are proposed, in which the effects of the competitive metabolic interactions described earlier are modified by the effects of bacterial association with the intestinal wall.