Biomedical subjects
Publications and source records attributed to R R Bollinger.
Although cimetidine is more effective than a placebo for the prophylaxis of stress-induced ulcers, it has no advantage over titrated antacid dosing. Several comparative studies even suggest that combining cimetidine with antacid is no more effective than use of full-dose antacid. Therefore, we recommend prophylactic use of cimetidine only when very large dosages of antacid are required, in order to minimize acid-base disturbances.
An analysis of data collected during the South Eastern Organ Procurement Foundation (SEOPF) Prospective Study from 1977-1982 was performed to identify the relative effects of different blood products on patient sensitization and graft survival in cadaveric donor renal transplant recipients. More than 2700 primary and 800 regrafted patients from 40 transplant centers were included in this study. A significant increase in actuarial graft survival was seen in primary recipients who had pretransplant transfusions with only frozen blood (P less than 0.003), washed blood (P less than 0.0005), packed blood (P less than 0.0001), or any combination of blood products (P less than 0.002) as compared with those who received no transfusions. No blood product was found to provide a significantly greater increase in graft survival than any other blood product. Likewise, regrafted patients had significant and equivalent increases in graft survival associated with each type of blood product examined. The increased graft survival associated with each blood product was the result of decreased graft rejection, and not apparently related to other differences among patients receiving different types of blood. Furthermore, the type of blood used in pretransplant transfusions did not significantly influence the degree of patient sensitization for first-graft recipients, although regrafted recipients who received packed blood or a combination of blood products showed a slightly greater degree of sensitization than those who received only frozen or washed blood. First-graft recipients given packed or mixed blood had a small, statistically insignificant increase of hepatitis B virus (HBV) antigenemia, compared with those receiving frozen, washed, or no blood. Regrafted patients given any type of transfusion had a 3-4-fold increased incidence of HBV antigenemia as compared with nontransfused patients, but this difference also was statistically not significant. These findings suggest that the benefits of increased graft survival and the risks of sensitization or HBV infection associated with pretransplant transfusions are not significantly affected by the type of blood used.
A review of more than 3000 cadaver donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to identify patients who received a transplant following a significant decrease in pretransplant sensitization as measured by the percentage of panel-reactive antibody (PRA). Such patients were identified as having had a most reactive (historical peak sera) PRA level at least 40 percentage points higher than their last sample tested prior to transplant (current sera). Additional data were obtained on 157 of these patients, who also had no history of pretransplant immunosuppression and had a negative pretransplant crossmatch with current sera. Data included the dates of pretransplant sera samples, the specific techniques used for each serum sample that was crossmatched or screened for PRA, and the serological results. The population studied included 17 of 87 first-transplant recipients and 17 of 70 regrafted recipients whose pretransplant crossmatches with peak sera were positive or not done. These subgroups showed no decrease in graft or patient survival compared with cohorts (70/87 first-transplant recipients and 53/70 regrafted recipients) for whom peak sera crossmatching was performed with negative results. Additional stratification for the techniques used in crossmatching and screening, as well as the interval between peak and current PRA levels, showed no significant associations with eventual graft or patient outcome. These results suggest that crossmatch testing using peak sera may not be important in predicting eventual graft or patient outcome for patients with a marked decrease in PRA prior to transplantation and a negative crossmatch with current sera.
Analysis of 2778 primary and 606 regrafted cadaveric donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to determine the influence of changes in presensitization on graft and patient outcome. Four mutually exclusive groups of patients were identified based on the relative difference in the percentage of panel-reactive antibody (PRA) from highest ever (peak) to most recent (current) pretransplant levels as follows: group 1 (unsensitized): peak = current PRA = 0; group 2 (rising or stable PRA): (peak = current PRA) greater than 0; group 3 (small decrease): (peak - current PRA) = 1-40%;) and group 4 (large decrease): (peak - current PRA) greater than 40%. First-transplant recipients in group 4 had significantly higher mortality when compared with groups 1-3 (P less than 0.002). This decrease in patient survival was evident at 6 months (81% +/- 4 vs 91% +/- 1) and persisted to three years (68% +/- 8 vs 78% +/- 2), and it was associated with a significant (P less than 0.037) increase in death from infectious causes. This finding was even more striking when only transfused recipients were considered: at three years the difference in patient survival was 63% +/- 11 vs. 77% +/- 2. In addition, transfused patients with a decrease in pretransplant PRA of greater than 40% had significantly lower overall graft survival (P less than 0.02) and a higher incidence of irreversible graft rejection (50% +/- 8 vs 33% +/- 1 at two years). For regrafted recipients, there were no differences in patient survival among groups, but those in group 4 had significantly lower graft survival (P less than 0.0033) than groups 1-3. These findings suggest that a substantial decrease in PRA prior to transplant does not necessarily indicate a decrease in potential donor alloreactivity, and in first-graft recipients it may reflect an increased susceptibility to life-threatening infections following transplantation.
Although the use of antithymocyte globulin/antilymphocyte serum (ATG/ALS) has been shown to be beneficial in treating renal allograft rejection, the incidence and nature of serum sickness reactions following such treatment have received limited attention. In the setting of rejection or infection, the diagnosis of serum sickness is often difficult on clinical grounds, and biopsy may be an undesirable means of obtaining documentation. A sensitive enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies against ATGAM (Upjohn) and was utilized in 35 patients treated for rejection with ATGAM following clinical unresponsiveness to bolus methylprednisolone therapy. Serum sickness was diagnosed clinically in 7 of these patients (20%) during or immediately following ATGAM therapy. Significant titers of anti-ATGAM antibody were found in these 7 cases, as well as 5 additional cases (14%). Upon retrospective review, the diagnosis of serum sickness was also made in each of these 5 additional cases based upon the immunopathologic detection of horse immunoglobulin deposits in vessels of tissue (lung or kidney) examined. In 2 other cases where serologic testing was negative, there was some clinical suggestion of serum sickness that could not be documented pathologically. ELISA for anti-ATGAM antibodies was negative in testing 46 control patients and pooled normal sera. In one case, retrospective testing of pre-ATGAM therapy serum samples showed significant antihorse antibodies. Despite a negative skin test prior to administration, this patient developed symptoms of serum sickness 15 days after the onset of ATGAM therapy. Extremely high titers of antibody were detected 5 days earlier (10 days posttherapy), and the presence of horse immunoglobulin immune complexes in the kidney was documented following graft loss that occurred within 4 weeks. These findings indicate (1) serologic testing for anti-ATGAM antibodies using a sensitive ELISA method provides a quick, inexpensive, noninvasive means for the presumptive diagnosis of serum sickness in complicated clinical situations, and (2) screening of patient sera prior to administration of ATGAM may be useful in avoiding potential serum sickness reactions.
The Organ Center establishes by the South-Eastern Organ Procurement Foundation collected information on 575 kidneys procured but not transplanted in the United States. The greatest proportion, 393, were not transplanted because a crossmatch-negative recipient was not found. Of these kidneys, 260 were transported to at least one additional center and 115 were offered to an additional center within 24 hr of removal. In 18 instances, attempts to share kidneys were made too late. The blood group representation of these kidneys was 62% A, 15% B, 12% AB, 11% O. The SEOPF system of crossmatches enabling the donor center to perform crossmatches on immunized recipients from 42 other transplant centers still resulted in the loss of 98 kidneys. However, this loss was half that predicted from the national experience. Rather than discarding them, 272 kidneys were transported overseas where 183 were transplanted. Technical problems related to the deceased, organ size, anatomic abnormalities, expended or nonviable material for tissue typing, and perfusion failure led to discarding 182 kidneys. Only 15 kidneys were reported injured irremediably at the time of removal, while 12 had bacterial contamination. The data emphasize our national problem and demand collaboration and new systems for kidney distribution in recipients of non-O blood groups.
We report the selective and therapeutic factors affecting multiple kidney transplant success from a prospective multicenter study of the South-Eastern Organ Procurement Foundation. From June 1977 to March 1982, 3,215 cadaver kidney transplants were performed at 39 institutions. There were 2,535 first, 564 second, 103 third and 13 fourth grafts. The actuarial graft survival rates at 1 and 2 years were 52 plus or minus 1 and 45 plus or minus 1 per cent, respectively, for first grafts, 44 plus or minus 2 and 40 plus or minus 3 per cent for second grafts, and 42 plus or minus 5 and 31 plus or minus 6 per cent for third grafts. Graft survival rates were significantly lower for second and third than for first transplants (p less than 0.003). There was no difference in patient survival rates. The data were analyzed to determine which selective and therapeutic variables governed success of primary and secondary grafts. Pre-transplant blood transfusions were associated with a significant increase in graft survival rates in primary (p less than 0.00005) and secondary transplants (p less than 0.01), and did not affect patient survival rates. The administration of antilymphocyte serum also improved graft survival rates significantly in primary (p less than 0.00005) and secondary grafts (p less than 0.00002), without alteration of patient survival rates. HLA compatibility improved primary graft survival rates (p less than or equal to 0.022) but this did not reach statistical significance in secondary graft survival rates. Second transplant graft survival rates were best when the primary graft functioned for more than 12 months (Breslow p less than or equal to 0.02) but were not related to the reason for loss of the first graft. Pre-transplant bilateral nephrectomy improved graft survival rates significantly but this phenomenon was linked to other treatment factors. No beneficial effect on graft survival rate could be shown after pre-transplant splenectomy in patients with primary or secondary grafts and this procedure was associated with reduced patient survival rates in both groups.
During the 4-year period from June 1977 to May 1981, a total of 108 patients with polycystic kidney disease and 2440 nonpolycystic patients received cadaver renal allografts in the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study. There were no significant differences between the groups with and without polycystic disease in terms of recipient blood group, history of splenectomy, or preformed antibody status. As a group, transplanted polycystic patients underwent native nephrectomy more often, had a better HLA match, received less antilymphocyte serum (ALS), and were slightly older than nonpolycystic patients. Although proportionately fewer polycystic patients received pretransplant transfusions than nonpolycystic patients (P = .002), transfusion was associated with a significant increase in graft survival in the polycystic group (P less than .05), as well as in the nonpolycystic group (P less than .0001). Gene frequency analysis showed no HLA-A, or -B antigen linkage with polycystic disease. No significant differences existed between the polycystic and nonpolycystic groups in terms of overall graft and patient survival. However, transplanted polycystic patients died more frequently from bacterial sepsis (P less than .05), especially from gram-positive organisms (P = .01). Pretransplant bilateral nephrectomy did not affect the incidence of sepsis. However, following graft failure, patients with bilateral native nephrectomy had a greater incidence of severe anemia (50% versus 39%) and death (58% versus 25%; P less than .05) than those with unilateral nephrectomy or no nephrectomy. Treatment with ALS did not significantly improve graft survival in those with polycystic disease. A strong positive correlation was found between patient death and treatment with ALS only in the polycystic group (P less than .01). These findings indicate that the use of pretransplant bilateral native nephrectomy and posttransplant ALS should be judicious in the polycystic patient because they may be associated with increased morbidity and mortality.
In the course of routine pretransplant cadaveric donor kidney biopsy examination, specimens from two donors were found to exhibit intense mesangial localization of IgA by immunofluorescence, with the presence of large immune complex-type deposits in these areas confirmed ultrastructurally. Both kidneys from each donor were transplanted with the ultimate result that three of the four kidneys underwent early irreversible rejection and were removed within 3 months, while the fourth kidney has maintained normal function for a period of 8 months. Morphological and immunofluorescent evaluation of the rejected kidneys at the time of nephrectomy showed minimal residual IgA mesangial deposits, but all had changes indicative of severe acute allograft rejection. These findings suggest that glomerular lesions involving mesangial IgA deposition can resolve fairly quickly following transplantation, but that the risk of irreversible acute rejection might be greater in the recipients of such kidneys.
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Fracture stabilization is often desirable prior to vascular repair in the management of major extremity injuries. This principle is particularly important when long vein grafts are required to minimize the risk of anastomotic disruption during the orthopedic portion of the procedure. However, in situations associated with prolonged periods of preoperative ischemia, early reperfusion of the injured extremity would be optimal. This report illustrates two cases of brachial artery injury in which heparin-bonded shunts were used to establish blood flow to the distal extremity before fracture fixation. The shunts were interposed between disrupted arterial segments and reestablished distal perfusion while associated fractures were internally stabilized. Thus, early revascularization allowed the orthopedic repair to proceed in an unhurried fashion. After adequate stabilization of the fracture, arterial reconstruction was completed using saphenous vein interposition grafts. This technique potentially could improve extremity salvage rates and facilitate the repair of arterial injuries associated with unstable long bone fractures.
A necessary step in the induction of unresponsiveness to transplantation antigens is the preparation and presentation of tissue antigens in a suitable form. A method is presented for obtaining rat histocompatibility antigen in a soluble, "heptenic" form suitable for coupling to a tolerogencie carrier. Lewis and ACI spleen cell membranes are solubilized with deoxycholate and purified by Lens culinaris affinity chromatography. The ultracentrifuged, solubilized preparation of rat histocompatibility (HC) antigen is unable to initiate immunity, but is able to react specifically with the product of an already established immune response. The HC antigen preparation is neither immunogenic nor tolerogenic alone. However, an antibody response to allogeneic cells can be prevented when these rat HC preparations are chemically coupled to tolerogenic carrier as described in the accompanying paper.
Histocompatibility (HC) antigens from Lewis (RT-11) and ACI (RT-1a) rats were solubilized and their tolerogenic potential alone or when conjugated to cellular carriers was investigated. The tolerogenic carrier potential of whole cells, crude membranes, and deoxycholate (DOC)-solubilized membranes was first determined by conjugating trinitrophenyl (TNP) groups to them and measuring their ability to prevent an anti-TNP plaque-forming cell response in rats after immunogenic challenge. Since whole lymphoid cells proved to be most effective in this system, DOC-solubilized allogeneic histocompatibility antigens were coupled to syngeneic lymphocytes, using carbodiimide cross-linking. Animals pretreated with this conjugate produced no alloantibody upon challenge with allogeneic cells. These results suggest that tolerance to allogeneic histocompatibility antigen can be produced by association of alloantigens on a tolerogenic self-carrier.
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The urinary excretion of free amino acids was measured in 15 men who participated in a continuous airborne alert for an extended period of time. These men made up one of three teams which took turns so as to assure that at least one team remained airborne in an EC-135J aircraft at all times during the 96-h alert. The team making up the test group herein reported was airborne for 8.5 h on each of four successive days; flights were flown during the daytime. The data strongly suggest that the participants experienced anticipatory stress during the early part of the first two flight days of the alert, after which the excretion of amino acids was virtually unaltered. Additionally, amino acid excretion during the 24-h period following the alert was essentially in accord with baseline values established for another groups of subjects.
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A biomedical appraisal of flight stress was made by means of a battery of urinary determinations on crewmen who participated in a 96-h airborne alert. The crewmen were divided into three teams, each consisting of 16 members and each manning an EC-135J aircraft. These teams took turns so as to assure that one team was airborne at all times during the alert; flights lasted either 8.5 or 12 h. Preflight baseline data were collected from only one of the three teams. Based on baseline and flight data obtained for that team, urea excretion correlated well with amino acid output which, in turn, correlated remarkably well with alpha-amino nitrogen output. These data collectively revealed the following flight effects: a) marked anticipatory stress immediately before the start of the airborne alert, b) marked flight stress late in each flight flown during the first 48 h, and c) adaptation to flight stress during the final 48 h.