Brief Therapy Based on Interrupting Ironic Processes: The Palo Alto Model

The model of brief therapy developed by Fisch, Weak-land, Watzlawick, and colleagues in Palo Alto is based on identifying and interrupting ironic processes that occur when repeated attempts to solve a problem keep the problem going or make it worse. Formulations of ironic problem-solution loops provide a template for assessment and strategic intervention, indicating where to look to understand what keeps a problem going (look for "more of the same" solution) and what needs to happen for the complaint to be resolved (someone must apply "less of the same" solution). Supporting research is preliminary but suggests this approach may be well suited for change-resistant clients.     

Prevalence of Autoantibodies to the p53 Protein in Autoimmune Hepatitis

The target antigens of anti-nuclear autoantibodies in autoimmune hepatitis (AIH) are poorly characterised. Since antibodies to the p53 nuclear protein have been reported in various autoimmune diseases, we have assessed the prevalence of these antibodies in patients with AIH (n = 45), primary biliary cirrhosis (n = 60), hepatitis B (n = 22), hepatitis C (n = 55), and in a control group of subjects with various non-liver diseases (n = 56). A significant proportion of patients with AIH (31%) had elevated levels of autoantibodies to the p53 protein. In contrast, the prevalence of these antibodies in primary biliary cirrhosis (8%) and viral hepatitis (6%) was similar to that in the control group (4%). The clinical features of the anti-p53 seropositive AIH patients were similar to those of the seronegative ones. Thus, the prevalence of p53 autoantibodies in AIH is higher than in other forms of chronic hepatitis, and may be useful in differential diagnosis.     

hTERT-immortalized prostate epithelial and stromal-derived cells: an authentic in vitro model for differentiation and carcinogenesis

Prostate cancer is the most commonly diagnosed type of cancer in men, and there is no available cure for patients with advanced disease. In vitro model systems are urgently required to permit the study of human prostate cell differentiation and malignant transformation. Unfortunately, human prostate cells are particularly difficult to convert into continuously growing cultures. We report here the successful immortalization without viral oncogenes of prostate epithelial cells and, for the first time, prostate stromal cells. These cells exhibit a significant pattern of authentic prostate-specific features. In particular, the epithelial cell culture is able to differentiate into glandular buds that closely resemble the structures formed by primary prostate epithelial cells. The stromal cells have typical characteristics of prostate smooth muscle cells. These immortalized cultures may serve as a unique experimental platform to permit several research directions, including the study of cell-cell interactions in an authentic prostate microenvironment, prostate cell differentiation, and most significantly, the complex multistep process leading to prostate cell transformation.     

Late influenza vaccination is associated with reduced effectiveness

BACKGROUND: Extensive research has been carried out to quantify the efficacy and immunologic responses to influenza immunization, however, only little was reported on whether the timing of vaccine administration affects its effectiveness. The study aims were to compare post-immunization hospitalization and mortality rates among high-risk patients who were vaccinated against influenza in different periods of autumn. METHODS: Data for the current population-based historical prospective study were obtained from a large health organization in Israel insuring 1,600,000 members. Study population (n = 68,166) included high-risk patients aged 55 and above, who were immunized against influenza between October and November 2003. RESULTS: Although at baseline, individuals vaccinated in late November (12-25/11/2003) were significantly younger and had lower burden of illness compared to those vaccinated in early October (1-13/10/2003), they had higher hospitalization rates and longer hospital stay during the following winter (December to March). They also had an increased risk for all-cause mortality (RR = 1.78; 95%CI: 1.13-2.80). No such differences were observed during the following summer (April-August). CONCLUSIONS: In countries where influenza generally peaks between December and early March, vaccines administered after mid-November might be less beneficial.     

Caregiving stressors and psychological distress among veteran resident and immigrant family caregivers in Israel

The study compared caregiving stressors and psychological distress between Israeli veteran resident and immigrant family caregivers. It examined whether psychosocial variables (appraisal of caregiving, mastery, social support and coping) mediate the differences in psychological distress between these two groups. A total of 213 veteran resident and 206 immigrant (from the former Soviet Union) caregivers of chronically ill elderly were recruited from health services. The comparisons between the two groups were examined separately for spouse and adult child caregivers. The immigrant spouse and adult child caregivers reported significantly higher levels of caregiving stressors than veteran resident caregivers, but psychological distress was significantly higher only among the immigrant adult child caregivers. In multivariate analyses, the difference in psychological distress disappeared when caregiving stressors and mediating psychosocial variables were included in the regression models. Different caregiving stressors and psychosocial variables were associated with psychological distress among the spouses and among the adult child caregivers. The findings suggest that the caregiving stressors and psychosocial variables explain differences in psychological health outcomes between veteran resident and immigrant caregivers. Social work interventions should address these factors among caregivers, take into account the relationship to the care recipient, be culturally adapted to the immigrant caregivers, and target immigrant adult child caregivers in particular.     

Visual impairment in children with epilepsy treated with vigabatrin

Vigabatrin is an anti-epileptic drug particularly useful for drug-resistant partial seizures and infantile spasms. Recently, vigabatrin-induced visual field constriction (VFC) and abnormal ocular electrophysiological studies were reported. In this study, we assessed visual fields, visual evoked potentials (VEPs), and electroretinography (ERG) in children treated with vigabatrin. Twenty-four visually asymptomatic children underwent a clinical ophthalmological examination, perimetry when appropriate, and VEP and ERG. Thirteen patients had at least one abnormal study. VFC was seen in 11 of 17 patients who had perimetry; 5 of 15 patients who underwent VEP testing and 4 of 11 who underwent ERG testing had abnormal examinations. For the most part, abnormal VEPs and ERGs were found in children who also had VFC. There was a consistent trend for longer treatment periods to correlate with VFC, abnormal ERGs, and VEPs. In summary, over half of the children treated with vigabatrin demonstrated VFC or abnormal ocular electrophysiological studies. Perimetry seemed to be the most sensitive modality for identifying vigabatrin toxicity. Abnormal ERGs and VEPs were primarily seen in children with VFC and may be useful in monitoring children who are not appropriate candidates for perimetry. Although the incidence of vigabatrin-induced VFC is worrisome, in the context of intractable seizures or infantile spasms, therapeutic benefits must be weighed against risks.     

Stress-induced dynamic changes in mouse brain polyamines. Role in behavioral reactivity

Recent findings indicate that rapid and transient changes in polyamine metabolism, termed the polyamine-stress-response, may occur repeatedly in the brain after chronic intermittent stress. Here, we sought to examine the effects of chronic intermittent restraint stress, or of daily intraperitoneal dexamethasone injections on polyamine concentrations in the hippocampus of adult male C57BL/6 mice. Additionally, we studied the effects of alpha-difluoromethylornithine, an irreversible ornithine decarboxylase inhibitor, on stress-induced changes in polyamines and on behavioral reactivity to novelty stress measured in an open-field arena. As previously observed, following a single stress episode putrescine concentration increased transiently, but the polyamines spermidine and spermine remained unchanged. Following chronic restraint stress, putrescine concentration was increased after each daily stress episode with the largest increase observed after the 4th episode, while spermidine was increased just after the 2nd and 4th episodes and spermine only after the 4th daily episode. In contrast, all polyamine concentrations were increased after 10 injections of either dexamethasone or vehicle (0.9% NaCl). A 14-day course of alpha-difluoromethylornithine treatment resulted in a complete putrescine depletion and over 50% reduction in polyamines, and led to changes in open field activity indicative of altered emotional behavior. CONCLUSIONS: (a) while putrescine concentration increases in the hippocampus after each restraint stress episode, spermidine and spermine undergo a delayed but transient increase; (b) in contrast, chronic dexamethasone treatment may lead to a permanent increase in the concentrations of all polyamines and; (c) chronic alpha-difluoromethylornithine treatment reduces brain polyamine concentrations and modulates emotional reactivity to novelty stress. The study indicates that the brain polyamine-stress-response is a dynamic process that varies with the type, intensity and length of stressful stimuli, and implicates this response as an adaptive mechanism in the reaction to stressors.     

Oncogenic transformation of normal enterocytes by overexpression of cyclin D1

Cyclin D1 plays an important role in the multi-step process of gastrointestinal tumorigenesis. We hypothesize that normal enterocytes over-expressing Cyclin D1 will demonstrate a transformed phenotype. The nontumorigenic intestinal epithelial cell line, IEC-18, was transfected with the vector pMV7-CCND1, encoding Cyclin D1. Three clones, with cyclin D1 levels similar to those seen in colon cancer cell lines, were further evaluated in comparison to the vector control cells. They proliferated faster and demonstrated anchorage-independent growth in soft agar, higher saturation density, and higher plating efficiency. When injected into nude mice, tumors were generated after 6–8 weeks. On the other hand these cells were more sensitive to induction of apoptosis. There was no change in the level of -catenin protein. In conclusion, Cyclin D1 can act as an oncogene in vitro and in vivo, when produced in immortalized normal intestinal epithelial cells. This model may be useful for understanding the role and interrelationships of Cyclin D1 in colorectal tumorigenesis.