Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis

Perforin delivers granzymes to induce target-cell apoptosis. At high concentrations, perforin multimerizes in the plasma membrane to form pores. However, whether granzymes enter target cells via membrane pores is uncertain. Here we find that perforin at physiologically relevant concentrations and during cell-mediated lysis creates pores in the target-cell membrane, transiently allowing Ca(2+) and small dyes into the cell. The Ca(2+) flux triggers a wounded membrane-repair response in which internal vesicles, including lysosomes and endosomes, donate their membranes to reseal the damaged membrane. Perforin also triggers the rapid endocytosis of granzymes into large EEA-1-staining vesicles. The restoration of target-cell membrane integrity by triggering the repair response is necessary for target cells subjected to cytotoxic T lymphocyte attack to avoid necrosis and undergo the slower process of programmed cell death. Thus, the target cell actively participates in determining its own fate during cell-mediated death.     

Impact of depressive symptoms on the treatment of generalized social anxiety disorder

Patients with depression are often excluded from studies on the treatment of social anxiety disorder (SAD), leaving gaps in our knowledge about the impact of depressive affect on treatment for SAD. Patients participated in a randomized, placebo-controlled study of treatment for SAD. As in previous studies, patients were excluded from the study if they met criteria for major depressive disorder in the past 6 months. This exclusion notwithstanding, patients who enrolled in the study exhibited a range of depressive symptoms, permitting an examination of the impact of depressive symptoms on treatment outcome for SAD. Assessment measures included the Clinical Global Impression Scale, Hamilton Rating Scale for Depression, Brief Social Phobia Scale, and Beck Depression Inventory. Higher levels of depressive symptoms were related to more severe social anxiety overall, and to less change in social anxiety symptoms over the course of the study. Patients who were deemed nonresponders to treatment had higher levels of depressive symptoms at pretreatment than those who responded. In addition, patients who dropped out of the study had higher levels of depressive symptoms at pretreatment than those who completed the study. These results suggest that modifications should be made to existing treatments to improve outcomes and decrease attrition in the substantial proportion of patients with SAD who also evidence depressive symptoms. Such modifications are likely to be more important when treating patients with SAD and comorbid major depressive disorder.     

Psychiatry in chronic pain: A review and update

As the field of pain management nears the halfway point of the Congressionally declared “Decade of Pain Control and Research,” the prevalence of chronic pain and disability related thereto continue to escalate. In the context of rising costs and suffering associated with persistent pain worldwide, the chronic pain research community has increasingly recognized and investigated the role of the cognitive and affective dimensions of pain. In this paper, the authors review psychologic aspects of pain, psychopathology in chronic pain syndromes, suicidality in this population, and the use of psychotropic medications for treatment in these patients. Where possible, the authors have outlined limitations of previous research in these areas, and have highlighted and described recent studies that have addressed these perceived shortcomings. The role of the psychiatrist in the treatment of patients with chronic pain is reviewed.     

Defining a cognitive function decrement in schizophrenia.

BACKGROUND: Although cognitive impairment is described as a core component of the characterization of schizophrenia, a sizable percentage of patients are classified as unimpaired by traditional definitions of impairment. The purpose of this study was to determine the percentage of patients with schizophrenia meeting criteria for a "cognitive function decrement" defined as a current level of cognitive function that falls below the level predicted by premorbid estimates. METHODS: Linear regression analyses were performed on a healthy control population to determine a predicted composite cognitive score based on maternal education, paternal education, and reading score as indicators of premorbid intellectual function. The percentages of patients with current cognitive function above and below predicted values were calculated. RESULTS: When the Wide Range Achievement Test-3 (WRAT-3) score and maternal education are both used to predict current cognitive performance, as expected, about half (42%) of control subjects fall below expectations. However, 98.1 % of patients fall below expectations. CONCLUSIONS: When cognitive function decrement is defined as a failure to reach the expected level of cognitive functioning, almost all patients with schizophrenia meet this definition.     

Monozygotic pregnancies from transfers of zona-free blastocysts

To minimize the risk of identical twinning the zona pellucida (ZP) was completely removed before blastocyst ET in all blastocyst transfers performed between May 1, 1999 and April 30, 2000. Compared to prior, zona intact, blastocyst transfers carried over between September 1, 1998 and April 30, 1999 no significant difference was noted regarding implantation, pregnancy, monozygotic pregnancy, or multiple gestation rates, thereby indicating that monozygosity can arise independently of the ZP.     

Acute caffeine intake before and after fatiguing exercise improves target shooting engagement time

INTRODUCTION: Previous research has identified acute caffeine ingestion as an effective aid in counteracting the decline in vigilance experienced during sentry duty and sustained operations. However, further research is needed to clarify caffeine's effects under various stressors and additional operational conditions. The purpose of the present study was to examine the effect of caffeine on target detection and rifle marksmanship during simulated combat operations. METHODS: There were 12 reservists who ingested 5 mg x kg(-1) body mass of caffeine (C) or placebo (P) 1 h before beginning a 2.5-h loaded march and 1.0-h sandbag wall construction task. Following exercise, participants were given a re-dose of 2.5 mg x kg(-1) body mass of C or P. An hour after ingestion, participants commenced a 2.5-h shooting session on a small arms simulator, which included friend-foe discrimination (FF) and vigilance (VIG) tasks. Marksmanship performance measures included engagement time (ET), the number of shots fired (NS), accuracy, and precision. RESULTS: C ingestion (initial and/or redose) did not affect shooting performance during the FF task. ET and NS improved during the VIG task with C ingestion (mean +/- SD of 2.82 +/- 0.27 s and 29.2 +/- 1.9 shots out of 30 targets, respectively) compared with the P trial (3.00 +/- 0.26 s and 28.0 +/- 3.0 shots; p < 0.05). CONCLUSION: Caffeine ingestion improves target detection and engagement speed during vigilance situations, but is not effective during more complex operations requiring higher levels of cognitive processing and fine motor control and coordination.     

Novel therapies

OBJECTIVE: To highlight selected research directed to new drug and device technologies to manage mucositis in cancer patients and to illustrate potential impact of successful therapies. DATA SOURCES: Published research articles and abstracts, clinical experience. CONCLUSION: Advances in molecular modeling of mucosal injury in cancer patients have created new opportunities for therapy. Research is analyzing the impact of single-agent interventions; varying degrees of efficacy are being reported. Once optimal dosing strategies for single-agent management are defined, the opportunity for multi-agent therapies will emerge. IMPLICATIONS FOR NURSING PRACTICE: The oncology nurse plays a pivotal role in assessing and managing mucositis in cancer patients.