Giavonni M. Lewis

An Immunologically Privileged Retinal Antigen Elicits Tolerance Major Role for Central Selection Mechanisms

Immunologically privileged retinal antigens can serve as targets of experimental autoimmune uveitis (EAU), a model for human uveitis. The tolerance status of susceptible strains, whose target antigen is not expressed in the thymus at detectable levels, is unclear. Here, we address this issue directly by analyzing the consequences of genetic deficiency versus sufficiency of a uveitogenic retinal antigen, interphotoreceptor retinoid-binding protein (IRBP). IRBP-knockout (KO) and wild-type (WT) mice on a highly EAU-susceptible background were challenged with IRBP. The KO mice had greatly elevated responses to IRBP, an altered recognition of IRBP epitopes, and their primed T cells induced exacerbated disease in WT recipients. Ultrasensitive immunohistochemical staining visualized sparse IRBP-positive cells, undetectable by conventional assays, in thymi of WT (but not of KO) mice. IRBP message was PCR amplified from these cells after microdissection. Thymus transplantation between KO and WT hosts demonstrated that this level of expression is functionally relevant and sets the threshold of immune (and autoimmune) reactivity. Namely, KO recipients of WT thymi generated reduced IRBP-specific responses, and WT recipients of KO thymi developed enhanced responses and a highly exacerbated disease. Repertoire culling and thymus-dependent CD25+ T cells were implicated in this effect. Thus, uveitis-susceptible individuals display a detectable and functionally significant tolerance to their target antigen, in which central mechanisms play a prominent role.

Secretion of D-aspartic acid by the rat testis and its role in endocrinology of the testis and spermatogenesis

The D‐isomer of aspartic acid (D‐Asp) has been found in rat testes. In the present study, samples of testicular venous blood plasma, rete testis fluid, interstitial extracellular fluid, luminal fluid from the seminiferous tubules, testicular parenchymal cells, epididymal spermatozoa and peripheral blood plasma were collected and analyzed for D‐Asp by two methods, an enzymatic and a chromatographic HPLC method. The two methods gave very similar results for all samples. The highest concentrations of D‐Asp (about 120 nmol/ml) were found in testicular venous blood plasma, with slightly lower concentrations in rete testis fluid (95 nmol/ml) and epididymal spermatozoa (80 nmol/g wet weight). Lower levels were found in testicular parenchymal cells (which would comprise mostly spermatids and spermatocytes), luminal fluid from the seminiferous tubules and interstitial extracellular fluid (26, 23 and 11 nmol/ml respectively). However, these values were all higher than those for peripheral blood plasma (6 nmol/ml). It would appear that D‐Asp is being secreted by the testis mostly into the venous blood, passing thence into the rete testis fluid and being incorporated into the spermatozoa at the time or after they leave the testis. The distribution of D‐Asp is thus quite different from that of testosterone, and its role and the reason for its high concentration in the male reproductive tract remain to be elucidated.

Pressure ulcers and risk assessment in severe burns.

Risk and incidence of pressure ulcers (PUs) in the burn population remain poorly understood. The purpose of this study was to determine the timing and incidence of PUs at our regional burn center and to identify early risk factors for PU development in burn patients. A retrospective review of 40 charts was performed from among the 1489 patients admitted to our regional burn center between January 2008 and December 2009. Twenty patients acquired PUs during their admission and were identified on the basis of International Classification of Diseases, ninth revision, designation, hospital stay >7 days, and thermal injury (excluding toxic epidermal necrolysis and purpura fulminans). The remaining 20 patients were matched controls based on ±5 years in age and ±8% TBSA. Patient, injury, and outcome characteristics were compared among patient groups using &khgr;2 for categorical variables and Mann-Whitney for continuous variables. The incidence of PU was 1.3% of all admissions. PU most commonly occurred at the sacrum/coccyx (eight), lower extremity (seven), and occiput (six). A majority of PU presented at stage 2 (33%), stage 3 (26%), and unstageable (30%). Thirteen were splint or device related and reportable. Ninety percent of patients with PUs presented with a Braden score of 16 or less (P = .03), although 60% of controls also had admission Braden scores less than 16. On an average, PUs were acquired within 17 days of admission. Data suggest burn patients are particularly at risk of developing PU based on admission Braden scores. However, low Braden scores do not necessarily correlate with eventual development of PU. Therefore, early and aggressive PU prevention and risk assessment tools must be used to diagnose PUs at an early and reversible stage.

Early Diagnosis and Prevention of Ischemic Enterocolitis in Massive Burns.

To summarize the most salient literature regarding the pathogenesis, diagnosis, and prevention of ischemic enterocolitis (IE) in thermal injury. IE is a poorly characterized gastrointestinal complication associated with large burns. This entity occurs irrespective of abdominal trauma. The diagnostic challenges, paucity of treatment options and related complications make IE particularly lethal. Herein we present a case of profound IE in a 40-year-old male who sustained 80% total body surface area (TBSA) burns. We provide an overview of our current understanding of IE, discuss early diagnostic strategies, and review possible treatment options. Although there are several promising biomarkers of early IE and potential treatment strategies, prospective studies are lacking. IE secondary to massive thermal injury is a lethal complication of severely burned patients. Early recognition and evidenced-based treatment strategies are paramount to successful management of patients with IE. Additional research and prospective trials are warranted given this devastating complication of massive burns.