Virtual reality as an adjunctive non-pharmacologic analgesic for acute burn pain during medical procedures.

INTRODUCTION: Excessive pain during medical procedures is a widespread problem but is especially problematic during daily wound care of patients with severe burn injuries. METHODS: Burn patients report 35-50% reductions in procedural pain while in a distracting immersive virtual reality, and fMRI brain scans show associated reductions in pain-related brain activity during VR. VR distraction appears to be most effective for patients with the highest pain intensity levels. VR is thought to reduce pain by directing patients' attention into the virtual world, leaving less attention available to process incoming neural signals from pain receptors. CONCLUSIONS: We review evidence from clinical and laboratory research studies exploring Virtual Reality analgesia, concentrating primarily on the work ongoing within our group. We briefly describe how VR pain distraction systems have been tailored to the unique needs of burn patients to date, and speculate about how VR systems could be tailored to the needs of other patient populations in the future.

Physical and psychologic rehabilitation outcomes for young adults burned as children.

OBJECTIVE: To report physical and psychologic outcomes for young adult survivors of pediatric burns. DESIGN: Prospective, correlational study. SETTING: Acute and rehabilitation pediatric burn care facility. PARTICIPANTS: Eighty-three young adult survivors of pediatric burns, who were 18 to 28 years of age, with total body surface area (TBSA) burns of 30% or greater, and were at least 2 years postburn. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Physical outcomes were assessed by muscle strength tests, grip and pinch measurements, mobility levels, and self-care (activities of daily living) skills. Psychologic outcomes included behavioral problems, personality disorder, and incidence of psychiatric illness. An individually administered Structured Clinical Interview for Diagnosis, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, for psychiatric diagnosis, was used to assess mental health, and behavioral problems were assessed with the Young Adult Self-Report. Participants reported educational achievement, employment status, state of transition from family of origin (home) to independent living, and pair bonding. The Short-Form 36-Item Health Survey and the Quality of Life Questionnaire were used to assess each participant's self-reported general health and quality of life. RESULTS: The majority of subjects had physical and psychologic outcomes that were within the normal range when compared with age-mates who had not experienced burns. The areas that were most likely to be impaired involved peripheral strength (wrist and grip). These deficits affected some self-care skills and correlated with TBSA. Standardized diagnostic interviews showed that greater than 50% of subjects qualified for a psychiatric diagnosis, with anxiety disorders as the most frequently occurring diagnosis. There were few significant correlations of the physical measurements or self-care skills with the burn size, psychologic problems, or social outcomes, and none appeared to be clinically important. CONCLUSIONS: Most of the people in this sample were functioning physically and psychosocially within normal limits as they reached adulthood. Although they appeared to function well as measured by standardized assessments, there were indications of private suffering that suggested they may not be functioning at an optimal level. The findings suggest that rehabilitation professionals could improve outcomes by including programs to develop overall muscle strength in severely burned children and by addressing concerns related to anxiety and other symptoms of psychologic distress.

Different types of glomerulopathic light chains interact with mesangial cells using a common receptor but exhibit different intracellular trafficking patterns.

Patients with plasma cell dyscrasias may have circulating light chains (LCs), some of which are nephrotoxic. Nephrotoxic LCs can affect the various renal compartments. Some of these LCs may produce predominantly proximal tubular damage, while others are associated with distal nephron obstruction (the so-called "myeloma kidney"). Both these are considered tubulopathic (T) LCs. A receptor has been found in proximal tubular cells (cubilin/megalin complex), which mediates the absorption of LCs and is involved in the pathogenesis of tubulopathies that occurs in these patients. Another group of nephrotoxic LCs is associated with glomerular damage and these are considered as glomerulopathic (G). These patients with G-LCs may develop AL-amyloidosis (AL-Am) or LC deposition disease (LCDD). Recent evidence indicates that the physicochemical characteristics (amino-acid composition and conformation of the variable region) of a given nephrotoxic LC may be the most significant factor in determining the type and location of renal damage within the nephron. Other factors may also be involved, including yet uncharacterized host factors that may include genetic polymorphism, among others. Interestingly, the amount of LC production by the clone of plasma cells does not correlate directly with the severity of the renal alterations. Understanding the nature of the interactions between G-LCs and mesangial cells (MCs) is crucial to define key steps that may be targeted for therapeutic purposes. Experimental studies have delineated important aspects pertaining to interactions between G-LCs and MCs, indicating that these interactions are receptor mediated. The data presented in the current study support a single receptor present on MCs for both LCDD and AL-LCs, as clearly demonstrated with competition and colocalization immunofluorescence (IF) studies. This receptor resides in caveolae present on the plasma membrane of HMCs and is overexpressed when HMCs are incubated with G-LCs but not TLCs. Caveolae play a fundamental role in receptor-mediated endocytosis, a crucial process in the internalization of AL-LCs and amyloidogenesis. LC internalization is clathrin mediated. The data also indicate that intracellular trafficking in MCs is different for AL-LCs and LCDD-LCs. AL-LCs are delivered to the mature lysosomal compartment where amyloid formation occurs. LCDD-LCs alter mesangial function and phenotype by interacting with the MC surface membranes through similar receptors as the AL-LCs. The data also demonstrated that cubilin and megalin were absent on MCs, so the receptor involved is different from the one already characterized in the proximal tubules.

Insights into mechanisms responsible for mesangial alterations associated with fibrogenic glomerulopathic light chains.

Our previous studies have shown that human mesangial cells (HMCs) incubated with fibrogenic glomerulopathic monoclonal light chains (G-LCs) obtained from the urine of patients with light chain deposition disease produce increased extracellular matrix (ECM) when compared with HMCs not exposed to fibrogenic LCs. This overproduction of ECM proteins is regulated by transforming growth factor-beta (TGF-beta); blocking TGF-beta normalizes the production of ECM proteins. All ECM proteins, after synthesis, have to go through the secretory pathway in the endoplasmic reticulum (ER) and Golgi complex for final maturation and secretion. Blocking the secretory pathway may reduce the accumulation of ECM proteins. We tested the effect of tunicamycin, a specific inhibitor of N-linked glycosylation in the ER which inhibited glycosylation and brefeldin A, an inhibitor of vesicle transport between the endoplasmic reticulum and the Golgi complex, on ECM protein production, both resulting in subsequent upregulation of glucose-regulated protein 78. Overproduction of fibronectin and tenascin by HMCs was normalized by tunicamycin and brefeldin A. Similarly, when HMCs were exposed to exogenous TGF-beta, the increase in fibronectin was reversed by tunicamycin and brefeldin A. Exogenous platelet-derived growth factor-beta (PDGF-beta) did not induce fibronectin overproduction but significantly stimulated proliferation of HMCs. In summary, this study further supports the notion that fibrogenic G-LCs promote the accumulation of ECM proteins, through the actions of TGF-beta. Importantly, the data indicate that altering protein trafficking in the ER results in impairment of secretion of proteins into the ECM. Furthermore, the data also reveal that PDGF-beta and TGF-beta act independently and that PDGF-beta activation by itself cannot increase ECM proteins directly, but only by increasing the number of HMCs.