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Biomedical subjects

R R Bollinger

Publications and source records attributed to R R Bollinger.

At least 91 records · Page 5Linked to original sources
PubMed1987

The influence of dose and dose rate of total lymphoid irradiation in the rat cardiac allograft model.

Immunosuppression generated by total lymphoid irradiation (TLI) may be of use in solid organ transplantation. We have investigated the use of TLI in the rat cardiac allograft model. Lewis rats received TLI from a cobalt-60 machine. The daily dose was 1.25 Gy and treatments were administered 4 days per week. We performed experiments to assess the effect of dose rate upon graft survival. The dose rate was varied by changing the source to animal distance and by using a lead attenuator. Cardiac allografts from each ACI donor rat were transplanted to the recipient Lewis rat's abdomen utilizing microvascular surgical technique. Heart graft survival times (GST) were monitored by direct palpation of the cardiac impulse. Immune function was measured by an activity index of the mixed lymphocyte reaction. In the absence of any immunosuppression there was a mean GST of 6.9 +/- 0.3 days. When a graft was placed the day following completion of TLI, there was an increase in GST as the total TLI dose was increased. Mean GST (+/- S.E.) following 5, 10, and 15 Gy were 12.3 +/- 1.3, 14.5 +/- 1.3, and 25.5 +/- 1.1 days, respectively. Following 20 Gy, GST decreased because of irradiation induced pulmonary toxicity and host death. When 3.5 weeks were allowed to elapse between the completion of TLI and transplantation, GST were less than those seen with equivalent doses of TLI and early transplantation. Mean GST following 5, 10, and 15 Gy and a delayed transplant were 7.2 +/- 0.1, 10.7 +/- 1.2, and 19.0 +/- 3.5 days, respectively. We tested the effect of dose rate upon GST.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Hepatic transplantation into sensitized recipients. Demonstration of hyperacute rejection.

Hepatic transplantation into humorally presensitized patients has occasionally been performed without reported accelerated rejection. To study survival of orthotopic hepatic transplants in sensitized recipients a series of studies in rats were performed. Lewis rats sensitized by three successive skin grafts from fully allogeneic ACI strain donors then underwent orthotopic hepatic transplantation from ACI donors. Nine of ten recipients died within 4 hr with bleeding from the liver surface. By comparison, nine unsensitized recipients survived a mean of 10.7 +/- 0.5 days before succumbing with cellular rejection. Death of the sensitized recipients was not due to coagulopathy or technical failure. Histological studies of hyperacutely rejected livers demonstrated marked hemorrhage, edema, congestion, and necrosis within the hepatic parenchyma. There was a relative lack of cellular infiltrate compared with livers rejected by unsensitized recipients. Immunofluorescent staining showed IgG bound to perivascular tissues and sinusoids, and complement bound to perivascular tissue. Serum from presensitized, but not control, recipients showed a high titer of donor-specific, complement-dependent cytotoxic activity. It is concluded that hyperacute rejection of hepatic transplants can occur in sensitized rats and is mediated by a humoral mechanism. The immunohistopathology of this process is described.

Animals↗
PubMed1987

Infiltrating cell phenotypes and patterns associated with hepatic allograft rejection or acceptance.

The association of inflammatory cell infiltration with orthotopic rat liver transplant rejection was studied by immunopathologic evaluation of allografts at different time points using high- and low-responder strain combinations. PVG(RT-1c) recipients of ACI (RT-1a) liver transplants had prolonged survival (greater than 100 days) without immunosuppression. In contrast, Lewis (RT-1l) recipients of ACI liver transplants had severe acute rejection with mean survival of 10.7 +/- 0.5 days (n = 9). Graft recipients of both strain combinations, as well as control syngeneic PVG-to-PVG and Lewis-to-Lewis graft recipients were sacrificed at various time points posttransplant. Sections of livers were evaluated in a masked fashion for histologic changes as well as the extent and phenotype of cellular infiltrates, as determined by immunoperoxidase labeling using monoclonal antibodies OX1 (pan leukocyte), W3/13 (pan T cell), W3/25 (T helper cell:Th), and OX8 (T cytotoxic-suppressor:Tc-s). The results suggest that: the intensity and relative distribution of rat hepatic allograft T cell infiltrates at a given time point do not necessarily correlate with eventual outcome; the intensities of W3/25 (Th) and OX1 (pan-leukocyte) cell infiltrates parallel each other in both high- and low-responder strain combinations; the relative ratio of T cells (W3/13) to non-T cells increases over time in low-responder strains but remains relatively constant in high-responder strains during active rejection; and the relative ratio of W3/25:OX8 (Th:Tc-s) decreases in high-responder strains but increases in low-responder strains.

Animals↗
PubMed1987

Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine.

Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA.

Animals↗
PubMed1987

Transplantation of the entire small bowel in inbred rats using cyclosporine.

Inbred strains of rats were used to analyze unidirectional host-versus-graft disease (transplant rejection) without graft-versus-host disease in small intestinal transplants and the immunosuppressive properties of cyclosporine (CsA). Forty-six Lewis rats received heterotopic transplants of the entire small bowel in four groups: Lewis-to-Lewis isografts, without CsA; Lewis-to-Lewis isografts, with CsA (15 mg/kg/day); (Lewis X ACI)F1-to-Lewis allografts, without CsA; (Lewis X ACI)F1-to-Lewis allografts, with CsA. Small bowel rejection was associated with gross morphological changes that preceded all other findings. A histologic scoring system assessed the degree of transplant rejection. A characteristic transient weight loss was seen in animals rejecting their bowels. Glucose absorption was impaired and polyethylene glycol absorption increased during rejection. Cyclosporine inhibited all of these changes in allografted rats. It is concluded that daily administration of cyclosporine is effective in preventing the morphologic and functional changes of acute transplant rejection in intestinal allografts and does not change these parameters in transplants that are not rejecting.

Animals↗
PubMed1987

Causes of death in renal transplant recipients. A review of autopsy findings from 1966 through 1985.

From 1966 through 1985, a total of 640 patients received 739 renal transplants at a single center transplantation program. Of 245 total deaths, a slide and chart review of all 116 autopsied cases (47%) identified the major causes of death as pneumonia (n = 43), sepsis (n = 32), hemorrhage (n = 15), peritonitis (n = 11), meningitis (n = 7), and pulmonary embolism (n = 5). Eighty-five (73.3%) of these patients died of complications directly associated with immunosuppression, almost all (n = 82) as a result of infection. Organisms most frequently identified at death were gram-negative bacilli (n = 72), Candida species (n = 23), cytomegalovirus (n = 17), enterococcus (n = 14), Staphylococcus aureus (n = 11), Aspergillus species (n = 10), Pneumocystis carinii (n = 5), and mycobacteria (n = 5). Significant associations were found between bolus steroid antirejection therapy and infection with Aspergillus cytomegalovirus. Diabetics had a higher incidence of fungal infections and bowel perforation than nondiabetics. During this 20-year period, overall one-year actual patient survival rates for the four respective five-year intervals increased dramatically (69.9%, 68.2%, 83.3%, and 91.8%), but the normalized death rate showed a smaller decrease for infectious vs noninfectious causes.

Adolescent↗
PubMed1987

Hemolytic anemia is not a frequent complication of ABO unmatched renal allografts from living related donors.

In summary, we could not document an increased incidence of HA nor a detrimental effect of CyA use in our recipients of ABO-unmatched LRD kidneys. Thus, it would appear that the incidence of HA in this situation is low enough that no special pretreatment of the kidney transplant or recipient is warranted. Since the long-term survival of ABO-unmatched LRD kidneys was equivalent to that of ABO-matched recipients there is no reason to select against them, or avoid the use of CyA. Rather a severe pretransplant anemia may predispose to a delayed recovery from anemia after transplantation.

ABO Blood-Group System↗
PubMed1985

Widely disseminated Cunninghamella mucormycosis in an adult renal transplant patient: case report and review of the literature.

A case of widely disseminated mucormycosis involving Cunninghamella bertholletiae is reported. This represents the first report of Cunninghamella infection in a transplant patient and, to our knowledge, only the eighth reported case of human infection by this saprophytic fungus. The clinical course was similar to most of the previously reported cases in that the patient was immunocompromised prior to the infection and the diagnosis was made too late for appropriate therapeutic intervention. The current case is unique in that it involved a renal allograft recipient; that the major clinical signs and symptoms mimicked myocardial infarction; and that there was more widespread dissemination than in earlier cases. The histologic and laboratory identification of the fungus are presented and correlated with the clinical parameters (signs, symptoms, and therapy) of this case as well as the cases previously reported in the literature.

Adult↗
PubMed1985

Renal allograft cell infiltrates associated with irreversible rejection.

All 74 renal transplant biopsies performed between 11/78 and 8/84 at Duke University and Durham VA Medical Centers having cellular infiltrates that could be phenotyped by immunoperoxidase labeling were examined to identify histologic and immunopathologic features which correlated with rejection. Monoclonal antibodies identifying hematopoietic cells, T cells, T helper cells, T cytotoxic-suppressor cells, macrophages, and B cells were used, and each phenotype population was graded separately based on pattern of infiltration: cortical-diffuse (CD), perivascular (PV), and cortical-aggregate (CA). Histologic and immunofluorescent studies were used to evaluate acute (humoral) and cellular types of vascular and interstitial inflammation. By univariate analysis, patients having irreversible rejection within 10 weeks postbiopsy (n = 23) had significantly higher grades of both acute vascular (humoral) inflammation and TC-S cell infiltrates in a CD pattern as compared with those who had good graft function. Multivariate (Cox regression) analysis was also performed considering biopsy changes, therapy before and after biopsy, and intervals between transplant, rejection onset, and biopsy--as well as other factors potentially affecting the biopsy or graft outcome. Of nine cell phenotype-pattern combinations, only TC-S infiltrates in a CD pattern were associated with a significant (P less than 0.03) relative risk (RR) of subsequent failure from rejection (RR = 8.2). When those cases with significant acute (humoral) inflammation (n = 10) were excluded, the relative risk of TC-S-CD infiltrates increased to 46.4 (P less than 0.04). These findings indicate that the location, as well as the number and type of cell infiltrates are critical in evaluating cellular forms of rejection, and that the extent of diffuse, cortical TC-S infiltration on biopsy provides the greatest predictor of subsequent irreversible graft failure.

Acute Disease↗
PubMed1985

Sensitivity and specificity of a monitoring test.

The usefulness of a diagnostic test is generally assessed by calculating the sensitivity and specificity, or the predictive value positive and predictive value negative of the test. When subjects are monitored periodically for evidence of disease, these calculations must incorporate the varying amounts of information per individual. If in addition, the test results lie on a continuous scale, these quantities vary with the cutoff value (cutpoint) used to define a positive test. They are usually calculated for a spectrum of potential cutpoints in order to produce receiver-operator characteristic curves. In this paper we use a partial likelihood solution to the discrete logistic model in order to obtain estimates of the diagnostic test indices and to provide a significance test when the diagnostic test is administered repeatedly to individuals.

Analysis of Variance↗