Small intestinal transplantation in nonhuman primates

Small intestinal transplantation represents a potentially therapeutic procedure for individuals with short gut syndrome. The purpose of this study was to develop a model for small intestinal transplantation in primates that is: technically feasible without microsurgery; consistent in the prevention of allograft rejection; functional in terms of nutrient absorption; and compatible with harvest for multiple organ procurement. First, autotransplantations on four rhesus monkeys were performed in order to study a variety of harvesting techniques and vascular anastomoses. Then, a study was performed with 14 heterotopic allotransplants in 4 baboons and 10 rhesus primates. The successful donor model consisted of division of the pancreas, harvesting the small bowel with a superior mesenteric artery and portal vein pedicle. The allograft vascular pedicle was anastomosed to the recipient's common iliac vessels in end-to-side fashion. The graft was transplanted as an out-of-continuity loop, both ends being exteriorized as stomas providing access for absorption studies and biopsy. Three immunosuppressive regimens were tested: (1) cyclosporine A (CyA) 20 mg/kg/d, solumedrol (SML) 2 mg/kg/d, and graft irradiation (150 rad) (n = 4); (2) CyA 20 mg/kg/d and SML 2 mg/kg/d (n = 3); and (3) CyA 40 mg/kg/d, SML 2 mg/kg/d, and azathioprine 5 mg/kg/d (n = 3). There were 4 deaths due to technical error in the first 24 hours. Weekly graft biopsy, serum CyA levels, complete blood count, and automated 24-channel serum analysis were performed. Grafts surviving greater than 14 days underwent absorption study via luminal perfusion with sucrose, maltose, dextrose, Pregestimil, xylose, and cyclosporine.(ABSTRACT TRUNCATED AT 250 WORDS)     

IDEC-131 (Anti-CD154), Sirolimus and Donor-Specific Transfusion Facilitate Operational Tolerance in Non-Human Primates

CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.     

Neurological manifestations of decompression illness in recreational divers - the Cozumel experience.

Neurological signs and symptoms are common in recreational divers with decompression illness (DCI). The spectrum of neurological manifestations, temporal profile, and laboratory findings are described in a large series of 200 consecutive recreational divers treated for DCI. The Hyperbaric Medicine Unit charts of 200 recreational divers treated for DCI were reviewed and analyzed. The cohort was mainly male, with a median age of 40 years, and quite experienced, with a median of 100 prior dives. In 44 divers (22%) a rapid ascent was documented. The median time to onset of neurological symptoms was 60 minutes after surfacing. One hundred seventy-seven of 200 divers (88.5%) had at least one symptom of neurological DCI at presentation. The most common neurological manifestations were paresthesia, dysesthesia, incoordination, motor weakness, and dizziness. Paresthesias were associated with significantly younger (p = 0.003) and less experienced (p = 0.03) divers. Similar but less significant correlations were noted for dysesthesias. Female divers were significantly more likely to experience painful skin symptoms (p < 0.001). Neurological manifestations are common in recreational divers treated for DCI. Neurological DCI and paresthesias are more likely to occur in younger and less experienced divers.     

The iliac crest cartilaginous cap

Bone and cartilage grafts can be procured from the ilium either separately or as composite chondroosseous grafts when sufficient cartilage is present. The thickness and anatomy of this iliac cartilaginous cap was analyzed in relationship to age in 50 individuals. Histology was that of normal hyaline cartilage. The cartilage alone was more pliable with little memory when compared with auricular or septal cartilage. The cartilage/bone junction was very strong. Cartilage thickness ran from close to 1 cm at age 5 to a diminished zero at age 25.     

Induction of major histocompatibility complex class II glycoproteins by interferon-gamma: attenuation of the effects of restraint stress.

The effect of restraint on the activation of macrophages was evaluated based on the induction of I-A expression following injection of viable Mycobacterium bovis (strain BCG) or treatment in vitro with recombinant interferon-gamma (rIFN-gamma). We found that restraint suppressed the induction of I-A expression when applied just prior to or at the same time as the injection of the microorganisms but had no effect if applied after the injection of the Mycobacteria. The effect of stress was attenuated by increasing the number of microorganisms or by incubating macrophages from stressed mice with higher doses of rIFN-gamma. The suppressive effect of restraint does not appear to be associated with uptake, processing or presentation of antigen but rather to an alteration in the response of the macrophages to rIFN-gamma.     

Oxygen Reverses Deficits of Cognitive Function and Memory and Increased Heart Rate Induced by Acute Severe Isovolemic Anemia

Background: Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse the effects of acute anemia.

Methods: Thirty-one healthy volunteers, aged 28 +/- 4 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test.

Results: Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia.     

Tensor fascia lata myocutaneous flap in lower abdominal wall reconstruction

The tensor fascia lata myocutaneous flap provides a reliable autogenous building block for anatomical lower abdominal wall reconstruction. Preservation of innervation allows maintenance of voluntary motor control and protective sensation. The excellent blood supply of this flap is particularly helpful in reconstructing previously irradiated areas. A one-stage repair is possible, leaving minimal secondary defect. We describe 4 patients illustrating the uses and versatilty of this flap. Anatomy, operative procedures, and indications for delay are also discussed.     

Characterization of ACTH mediated suppression of MHC class II expression by murine peritoneal macrophages.

The effect of ACTH on the expression of major histocompatibility complex (MHC) class II (I-A) glycoprotein by murine peritoneal macrophages was evaluated. ACTH suppressed the expression of I-A by macrophages in a time- and dose-dependent manner. ACTH mediated its effect by decreasing the level of I-A mRNA. ACTH suppressed the expression of I-A by macrophages from mice that are susceptible to the in vivo growth of mycobacteria but did not affect the expression of I-A by macrophages from Mycobacterium bovis strain (BCG)-resistant mice. The concentrations of ACTH required to suppress I-A expression were greater than that required for an effect on adrenal steroid production and may be related to the localized production of ACTH by lymphocytes and macrophages.     

Quantification of flow through an interatrial communication. Application to the partial Fontan procedure.

The partial Fontan procedure has become an accepted alternative for the high-risk candidate. Creation of a small right-to-left shunt will lower the systemic venous pressure and improve systemic cardiac output while maintaining an acceptable systemic arterial saturation. However, because of variations in patient size and postoperative transpulmonary gradient, proper sizing of the residual defect is difficult. We have therefore conducted a series of experiments on a model that simulates the blood flow across interatrial defects of varying sizes at several pressure gradients. We used porcine blood to develop guidelines for the sizing of the residual defect. Our results demonstrate a linear relationship between flow and pressure gradient across all hole sizes tested. In addition, there was a linear relationship between atrial septal defect size and flow at each pressure gradient. Our data show that the Gorlin formula predictions overestimated flow by 10% to 40%. It is evident from these data that relatively small changes in the size of the atrial septal defect or in the pressure gradient result in significant changes in flow. Therefore we advocate the use of an adjustable interatrial communication such as the snare-controlled adjustable atrial septal defect for patients undergoing partial Fontan procedures.