Nutrient-related issues affecting successful experimental orthotopic small bowel transplantation

BACKGROUND: This study tested the effectiveness of a nutrient-rich preservation solution in a small animal model of orthotopic whole small bowel transplantation. METHODS: Lewis rats received syngeneic total orthotopic small bowel graft after cold storage for 6 h. Donor small bowel was flushed vascularly with University of Wisconsin (UW) solution and flushed luminally with UW solution or an amino acid-rich (AA) solution as follows: Group 1, no luminal flush; Group 2, UW solution; Group 3, AA solution. Biopsies were taken over 14 days posttransplant; energetics, oxidative stress, neutrophil recruitment and histologic injury were assessed. RESULTS: All animals in Groups 1 and 2 failed to survive 12 h posttransplant due to hemorrhagic shock and fluid loss. In contrast, all animals in Group 3 survived the operation; survival after 14 days was 80% (4/5). In Group 3, full recovery of tissue adenylates (ATP and energy charge) to freshly isolated tissue values occurred within 3 days. Oxidative stress as assessed by malondialdehyde (MDA) levels was low in Group 3 throughout 14 d; Groups 1 and 2 exhibited high oxidative stress over the initial 35 min reperfusion (P<0.05). Neutrophil recruitment (myeloperoxidase activity) was significantly reduced in Group 3 tissues, as was histologic injury (P<0.05 compared to Groups 1 and 2). By day 14, Group 3 exhibited complete mucosal restoration. CONCLUSIONS: The data presented in this communication supports the use of an intraluminal preservation solution that is tailored to the metabolic requirements of the small bowel.     

Urolithiasis - nutritional aspects

The progressive increase in the incidence of calcium oxalatephosphate calculi of the upper urinary tract during the 20th century in Western Europe and North America appears associated with affluence. Changes in diet over that time period have produced changes in urinary solutes which would increase the probability of calculus formation. Increased ingestion of animal protein produces a significant increase in the urinary excretion of calcium, oxalate and uric acid. Dietary calcium, oxalate and purine increase the excretion of calcium, oxalate and uric acid directly. Urine oxalate also increases with an increased ingestion of calcium but, paradoxically, also increases with severe dietary calcium restriction. Oral carbohydrate loading increases urinary calcium and magnesium excretion. Changes in urinary calcium excretion induced by dietary fiber appears related to the phytate content. A rational, though not of proven efficacy, dietary approach to urolithiasis therapy includes restriction of animal protein, avoidance of excess oxalate ingestion, a normal calcium intake, and water intake sufficient to generate 2 liters of urine per day.     

Comparison of techniques to determine continence zone

The urethral pressure profiles for 36 patients were analyzed specifically for continence zone by 3 techniques: 1) triangle, 2) planimeter and 3) weight. Graphically, the best agreement was between the weight and planimetry methods but, statistically, there was a significant difference among techniques except for the subgroup that had the smallest continence area.     

Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease

Experimental evidence from animal models has provided a framework for our current understanding of autoimmune disease pathogenesis and supports the importance of genetic predisposition, molecular mimicry, and immune dysregulation. However, only recently has evidence emerged to support the role of immune dysregulation in human organ-specific autoimmune disease. In the current study of the "late" manifestation of autoimmune thyroid disease (AITD) in a cohort of human immunodeficiency virus (HIV)-positive patients following highly active antiretroviral therapy (HAART), we discuss how immune dysregulation and factors associated with the immunopathology of HIV infection fit the current understanding of autoimmunity and provide a plausible basis for our clinical observations. De novo diagnoses of thyroid disease were identified between 1996 and 2002 in 7 HIV treatment centers (5/7 centers completed the study). Patients were diagnosed as clinical case entities and not discovered through thyroid function test screening. Paired plasma specimens were used to demonstrate sequential rise in thyroid antibodies.Seventeen patients were diagnosed with AITD (median age, 38 yr; 65% were of black African or black Caribbean ethnicity; and 82% were female). The median duration of immune reconstitution was 17 months. Graves disease (GD) was diagnosed in 15 of 17 patients. One patient developed hashithyrotoxicosis with atypically raised C-reactive protein, and another developed hypothyroidism. One GD patient had associated secondary hypoadrenalism. The estimated combined prevalence of GD for 4 treatment centers for female patients was 7/234 and for males was 2/1289. The denominator numbers were matched controls, from 4 centers able to provide data, who commenced HAART during the same time (January 1996 to July 2002) and who did not develop clinical AITD. The mean baseline pre-HAART CD4 count was 67 cells/mL, and the mean increase from nadir to AITD presentation was 355 cells/mL. AITD patients were more likely than controls (95% confidence interval, chi-square test) to be severely compromised at baseline (as defined by a CD4 count < 200 cells/mL or the presence of an acquired immunodeficiency syndrome [AIDS]-defining diagnosis), and to experience greater CD4 increments following HAART. AITD may be a late manifestation of immune reconstitution in HIV-positive patients taking HAART, and immune dysregulation may be an important factor.     

Astrocyte specific viral strains in HIV dementia

We molecularly characterized human immunodeficiency virus type 1 (HIV-1) present in pure populations of astrocytes, macrophages, and multinucleated giant cells isolated using laser capture microdissection from brain tissue of two patients who died with HIV-associated dementia. The V3 region of the HIV-1 envelope (env) gene was amplified from the pure-cell populations, and multiple clones were sequenced. In both patients, the V3 env sequences were distinct in astrocytes compared with neighboring macrophages or multinucleated giant cells and were characteristic of CCR5-using (R5) HIV-1. These results demonstrate cell-specific compartmentalization of distinct R5-like viral strains in the central nervous system microenvironment.