Pre-transplant low level HLA antibody shows a composite poor outcome in long-term outcome of renal transplant recipients.

To determine the significance of low-level DSA (donor specific antibody) in patients transplanted with negative cytotoxicity AHG (antihuman immunoglobulin) crossmatch, data from 279 patients who received a kidney transplant between July 1999 and March 2006 were collected. All kidney recipients received ABO-compatible donors. A poor outcome was defined as any one of the following: death, Cr>2.0 mmol/L, occurrence of a rejection episode. Luminex Screening and Single Antigen assays from Tepnel Life Codes were used to detect human leukocyte antigen antibodies on pre-transplant sera retrospectively. Twenty-four out of 279 recipients demonstrated the presence of solid-phase DSA (MFI>1000) present pre-transplant. In DSA+ group, the accumulated good versus poor outcome rate was 0.30 versus 0.70, respectively. These rates were 0.49 and 0.51, respectively, in the DSA- group. The difference in composite poor outcome between DSA+ versus DSA- group was significant (p=0.030). The DSA- group had no difference in patient survival as compared to the DSA+ group (p=0.061). There is no statistically significant difference for either mortality or outcome results between high MFI (>2000) and low MFI (≤2000) groups. Our data suggest that solid-phase antibodies which are not strong enough to elicit a positive T-AHG crossmatch may influence long-term graft outcome.

Preoperative stress conditioning prevents paralysis after experimental aortic surgery: increased heat shock protein content is associated with ischemic tolerance of the spinal cord.

BACKGROUND: All forms of surgical therapy are stressful and injurious. The problems of paralysis, renal dysfunction, and colonic ischemia associated with aortic occlusion are due to acute ischemia-reperfusion injury at the cellular level. Acute-anterior spinal cord ischemia is the most devastating outcome of these iatrogenic-ischemic events. The majority of surgical procedures are performed electively and therefore provide an opportunity to preoperatively condition the patient to minimize these ischemia-related morbidities. OBJECTIVES: We sought to determine whether acute spinal cord injury associated with aortic occlusion can be prevented by induction of the cellular stress response by means of preoperative administration of whole-body hyperthermia or stannous chloride. METHODS: The study consisted of an experimental rabbit model of infrarenal aortic occlusion for 20 minutes at normothermic body temperature. RESULTS: Control rabbits experienced an 88% (7/8) incidence of paralysis after spinal cord ischemia induced by 20 minutes of aortic occlusion, whereas animals treated preoperatively with either whole-body hyperthermia (0/9) or stannous chloride (0/4) never became paralyzed (P <.001 for control vs treated groups). Ischemic protection of the spinal cord was associated with increased content of stress proteins within tissues of pretreated animals. CONCLUSION: Prior induction of the heat shock response in the whole animal will increase the content of stress proteins within the spinal cord and other tissues and result in the prevention of hind-limb paralysis associated with aortic occlusion. We have designated the preoperative induction of the cellular stress response for the prevention of ischemic tissue injury stress conditioning. We suggest that stress-conditioning protocols represent the opportunity to practice preventative medicine at the molecular level.

In vivo characterization of the molecular-genetic changes in gastric mucosa during the development of acute gastritis and stress ulceration.

BACKGROUND: Trauma patients are at risk for the development of stress ulceration. Stress ulceration should be associated with increased heat-shock gene (iHSP70) and an inhibition of the trefoil peptide, spasmolytic polypeptide (SP), and mucin (MUC5AC) gene expressions. METHODS: Male Sprague-Dawley rats (10 weeks old) were restrained for 0-, 4-, 8-, 12-, and 24-hour periods of time. Gastric ulcers were graded using a one- to three-point scoring system. The level of mucosal gene expression was determined at each time point for three genes: iHSP70, SP, and MUC5AC. RESULTS: Gastric ulceration developed in direct proportion to the duration of restraint. Gastric ulceration was preceded by increased iHSP70 and decreased SP and MUC5AC gene expressions. CONCLUSION: Restraint-induced gastric ulceration was preceded by an up-regulation of iHSP70 and a down-regulation of SP and MUC5AC gene expressions.