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Biomedical subjects

D C Dafoe

Publications and source records attributed to D C Dafoe.

At least 55 records · Page 3Linked to original sources
PubMed1996

Human syngeneic intestinal transplantation: evaluation of enterocyte viability with serum levels of intestinal fatty acid binding protein.

In a case of human syngeneic intestinal transplantation, the post-operative course was complicated by the Systemic Inflammatory Response System (SIRS). This syndrome was characterized by negative cultures and elevated levels of the pro-inflammatory cytokines, IL-1 beta, IL-6 and TNF. In keeping with current concepts of translocation across the enterocyte barrier as the etiology of SIRS, levels of intestinal fatty acid binding protein (I-FABP), an enterocyte-specific protein, also increased. These observations suggest that (i) a clinical syndrome consistent with translocation may occur in the absence of rejection in intestinal transplantation, and (ii) I-FABP may serve as a clinically relevant marker for enterocyte injury.

Adult↗
PubMed1996

Volume-mediated pulmonary responses in liver transplant candidates.

Pulmonary hypertension, defined as mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg, is a recognized complication of hepatic dysfunction with portal hypertension and is considered a relative contraindication to liver transplantation. To characterize pulmonary hemodynamic responses in OLT candidates without pre-existing primary pulmonary hypertension, 22 consecutive patients referred for OLT at the Stanford University Hospital underwent prospective right heart catheterization with pressure determinations at baseline and following infusion of 11 crystalloid over 10 min. In addition, EKG, chest X-ray and transthoracic echocardiograms were performed as a part of the routine evaluation. Eleven non-cirrhotic patients served as controls. At baseline, 1/22 (4.5%) OLT patients had pulmonary hypertension while 9/22 (41%) developed pulmonary hypertension following volume infusion (p < 0.0001). In contrast, 0/11 controls manifested elevated pulmonary pressures at baseline or following volume challenge. OLT candidates were found to have significant increases in mean pulmonary pressure and capillary wedge pressure (PCWP) compared to controls, suggesting intravascular volume overload or left ventricular dysfunction as potential causes. OLT candidates who manifested volume-dependent pulmonary hypertension (a) had a 2-fold higher baseline PCWP, (b) currently smoked, and (c) had previously undergone portosystemic shunts. Aggregate analysis of EKG, echo and CXR for determination of volume-mediated pulmonary hypertension revealed a sensitivity of 25%, specificity of 75% and a positive predictive value of 40%. Preoperative identification of patients with a predisposition to manifesting elevated pulmonary pressures in the context of rapid volume infusion offers the potential for improved risk stratification and optimized clinical management.

Adult↗
PubMed1995

Tolerance induced by direct inoculation of donor antigen into the thymus in low and high responder rodents.

A novel approach to tolerance induction in rats was recently described where donor antigen is inoculated directly into the thymus along with a brief period of immunosuppression in a pretransplant strategy. To develop a strategy that has more clinical appeal, we evaluated the timing of donor antigen inoculation in relation to allografting, the use of frozen bone marrow as the antigen, and the dose response of purified T cells as the antigen in a low responder heterotopic heart allograft combination. Additionally, the success of this pretransplant strategy in different low and high responder strain combinations was defined. In tolerant low responder animals we evaluated in vitro and in vivo cellular immunity. Tolerant host strain naive CD8+ T cell responses to donor and third party stimulators were compared to determine if tolerance is related to the strength of the response of the T cell subsets to donor antigen. Frozen bone marrow can induce tolerance in a low responder combination. Additionally, the dose of purified T cells necessary for tolerance induction was 5 x 10(5) cells. The pretransplant strategy was successful in two low responder strain combinations, Lewis into Wistar Furth and Lewis into DA, but unsuccessful in all high responder strain combinations evaluated. Low responder animals unresponsive to donor heart allografts demonstrate intact cell-mediated immunity and donor-specific tolerance in vivo by rejecting third party but not second donor strain hearts. The in vitro responses of tolerant animals demonstrated donor-specific suppression of the MHC class II response but an intact (normal) response to third party stimulators by proliferation assays and IFN-gamma production, suggesting suppression at the CD4+ T cell subset level.

Animals↗
PubMed1995

A comparison of spontaneous versus induced tolerance in an experimental model of rat hepatic allograft transplantation.

In some rodent haplotype combinations, spontaneous tolerance (ST) develops after orthotopic liver transplantation (OLT) without any immunosuppression [e.g., Lewis (Lew, RT1) into Wistar Furth (WF, RT1u)] whereas in other combinations vigorous, progressive rejection rapidly leads to the death of the recipients. We (and others) have induced tolerance (IT) in a rejecting strain combination [Dark Agouti (DA, RT1a) into Lew] by intrathymic inoculation of donor bone marrow cells and 1 cc of antilymphocyte serum (ALS) 7-14 days prior to OLT. We hypothesized that cellular immunity in the two groups of animals was similar. We first compared survival in each group of animals and found that there was no difference in the number of animals surviving > 100 days (8/11 vs 16/17, ST vs IT, respectively, P = 0.11). Liver function studies were similar in these animals at 2 and 4 weeks after OLT and comparable to syngeneic Lew into Lew OLT animals, but significantly lower than in the rejecting DA into Lew combination treated with only ALS. Animals that were unresponsive to their allografts demonstrated donor-specific tolerance by the acceptance of donor strain (n = 4, ST and IT) and rejection of third party (n = 1 and n = 2, ST and IT groups, respectively) heterotopic heart allografts. One-way mixed lymphocyte cultures (MLC) of peripheral blood lymphocytes against donor and third party antigen were suppressed to donor and third party stimulators versus the MLC of unmanipulated animals. Naive host strain responder lymph node cells and purified T cells demonstrated strong proliferative responses to donor strain antigen in both the ST and IT animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Intraportal delivery of immunosuppression to intrahepatic islet allograft recipients.

Local delivery of immunosuppressive agents may dampen local alloreactive events with avoidance of systemic toxicity. We investigated the innovative strategy of intraportal (IPO) delivery of three immunosuppressive agents in streptozotocin diabetic rat recipients of islet allografts (Lewis to Wistar-Furth) transplanted intrahepatically. IPO budesonide (BUD, 240 or 360 micrograms/kg per day), a potent steroid, and cyclosporin (CyA, 2 or 4 mg/kg per day) did not prolong graft mean survival time [MST +/- standard deviation (SD)] as compared to nonimmunosuppressed recipients. Fourteen days of IPO FK 506 (0.16 mg/kg per day) significantly increased MST as compared with untreated controls (49 +/- 29 vs 7 +/- 1 days, P < 0.01) and was more effective than intravenous (IV) FK 506 (17 +/- 7 days, P < 0.01). When FK 506 was given for 28 days, the benefit of IPO over IV delivery was reaffirmed (MST 81 +/- 32 vs 34 +/- 4 days, P < 0.01). The potential for toxicity was lessened by lower mean systemic levels in the IPO group as compared to the IV group (1.3 +/- 0.6 vs 3.5 +/- 0.9 ng/mg, P < 0.02). The strategy of continuous IPO FK 506 was effective in the prevention of rejection of intrahepatic islet allografts.

Animals↗
PubMed1995

Orthotopic liver transplantation with selective use of venovenous bypass.

BACKGROUND: To determine the utility of selective use of venovenous bypass (VVB), an algorithm based upon hemodynamic criteria was instituted at Stanford University Medical Center: the bypass was used if the systolic blood pressure decreased below 100 mm Hg with a trial of caval and portal clamping. PATIENTS AND METHODS: Eleven consecutive patients underwent orthotopic liver transplantation (OLT) with use of VVB on a selective basis; using the hemodynamic exclusion criteria, none required VVB. A group of 20 patients undergoing OLT with VVB served as historical controls. RESULTS: Overall patient and graft survival were identical in both groups (75%). Avoidance of VVB decreased operative and warm ischemia time and decreased peak transaminase and total bilirubin values, but increased rates of intraoperative blood loss. However, the absolute numbers of blood products administered were not different between groups. CONCLUSION: Selective use of VVB for OLT does not incur increased morbidity or mortality. Potential advantages include cost savings with decreased operative and anesthetic time.

Adult↗
PubMed1995

Magnetic resonance imaging-derived parameter of portal flow predicts volume-mediated pulmonary hypertension in liver transplantation candidates.

BACKGROUND: Pulmonary hypertension is a source of perioperative mortality after orthotopic liver transplantation (OLT). The purpose of this study is to (1) characterize the pulmonary hemodynamic response in OLT candidates, and (2) determine whether portal flow index (PFI), a magnetic resonance imaging (MRI)-derived parameter, is a useful predictor of the pulmonary hemodynamic response. METHODS: Twenty-five consecutive OLT candidates underwent right heart catheterization with pressure measurements at baseline and after infusion of 1 L of crystalloid. MRI, chest roentgenography, electrocardiography, and echocardiography were also performed as routine screening techniques. Sixteen patients in intensive care unit with normal liver function served as controls. RESULTS: After volume infusion, pulmonary hypertension (mean pulmonary artery pressure greater than 25 mm Hg) developed in 9 of 25 OLT candidates with elevations in both pulmonary capillary wedge and mean pulmonary pressures. In contrast, 0 of 16 controls experienced pulmonary hypertension (p < 0.01). Although routine modalities did not predict this hemodynamic response, PFI had a 94% specificity and 78% sensitivity. CONCLUSIONS: OLT candidates exhibit volume-induced pulmonary hypertension with responses suggestive of left ventricular dysfunction. The significance of this observation is unknown, but the MRI-derived parameter, PFI, may serve as a screening technique to limit catheterization to a select group of OLT candidates.

Adult↗
PubMed1995

Magnetic resonance imaging and hepatic hemodynamics: correlation with metabolic function in liver transplantation candidates.

BACKGROUND: Preoperative assessment of orthotopic liver transplantation candidates requires definition of both the anatomy and metabolic function of the native liver. Current evaluation techniques combine computed tomographic scanning, duplex ultrasonography with blood chemistry analysis, and physical stigmata of end-stage liver disease. Recently, magnetic resonance imaging (MRI) has emerged as an alternative method for delineation of hepatic and portal venous anatomy. In addition, MRI accurately measures hepatic volume and portal venous blood flow. METHODS: To examine the role of MRI-derived indexes of hepatic hemodynamics in the preoperative assessment of liver function, 39 consecutive liver transplantation candidates were studied in a prospective manner. Liver function (aspartate aminotransferase), alanine aminotransferase, alkaline phosphatase, total bilirubin, and albumin levels), hematologic indexes (complete blood cell count, prothrombin time), and Child's classification were determined at the time of evaluation. Axial breath-held multiplanar spoiled-gradient echo MRI measured hepatic volume, whereas a cine phase-contrast sequence perpendicular to the portal vein measured flow. RESULTS: Hepatic index, defined as hepatic mass corrected for body surface area, was found to correlate with prothrombin time (p < 0.04) and platelet count (p < 0.03) by multivariate regression analysis. Portal flow index (PFI), defined as portal flow corrected for hepatic mass), was associated with aspartate aminotransferase (p < 0.02), alanine aminotransferase (p < 0.04), and albumin (p < 0.03) by multivariate regression analysis. In addition, PFI was closely correlated with the patients' functional status as determined by Child's classification system. Increasing values of PFI were associated with declining hepatic functional reserve. Child's class A patients had a mean PFI that was two times less than that of Child's class B patients (0.26 +/- 0.04 versus 0.04 +/- 0.06 ml/min/gm; p < 0.02) and five times less than that of Child's class C patients (0.26 +/- 0.04 versus 1.05 +/- 0.14 ml/min/gm; p < 0.001). Similarly, the mean PFI associated with Child's class B was two times less than that of Child's class C (0.46 +/- 0.06 versus 1.05 +/- 0.14 ml/min/gm; p < 0.01). These data show that MRI-derived indexes of portal hemodynamics and hepatic mass (1) correlate well with biochemical indexes of hepatic dysfunction and (2) serve as anatomic and hemodynamic correlates to Child's functional classification. CONCLUSIONS: We conclude that MRI may serve to noninvasively delineate preoperative hepatic vascular anatomy and metabolic dysfunction in candidates undergoing examination for liver transplantation.

Adult↗
PubMed1995

Cytochrome P450IIIA activity and cytokine-mediated synthesis of nitric oxide.

BACKGROUND: Although nitric oxide synthase (NOS) is a cytochrome P450-like hemoprotein with additional sequence homology to cytochrome P450 reductase, the role of the cytochrome P450 system in cytokine-mediated NO synthesis is unknown. METHODS: To characterize the role of the P450 system in the synthesis of NO, NO production, NOS enzyme activity, and steady state NOS mRNA and protein expression were characterized in the setting of P450 isoform activity inhibition by using a model of isolated rat hepatocytes in primary culture. Cimetidine (0 to 10 mmol/L) was chosen as a specific inhibitor of P450IIIA activity. NO production was induced by interleukin-1 (50 ng/ml) and tumor necrosis factor (500 units/ml) and quantified by measurement of its metabolite, nitrite, in the culture medium. Steady state NOS mRNA and protein expression were determined by reverse-transcriptase polymerase chain reaction and immunoblot analysis, respectively. NOS enzyme activity was measured by the conversion of tritiated-L-arginine to tritiated-L-citrulline. RESULTS: Inhibition of P450IIIA activity was associated with a concentration-dependent decrease in cytokine-mediated NO production. Levels of NOS mRNA and protein were not altered. The NOS enzyme assay was notable for stable concentrations of intermediate, N-OH-L-arginine, and decreased production of the final end product, L-citrulline. Dixon plot kinetic analysis of cimetidine-mediated inhibition of NOS yielded an inhibition constant Ki = 1.76 mmol/L. CONCLUSIONS: These results indicate that cytochrome P450IIIA isoform may play a posttranslational role in cytokine-mediated NO synthesis in this model of isolated rat hepatocytes in primary culture.

Amino Acid Oxidoreductases↗
PubMed1995

Interferon-gamma and interleukin-10 messenger RNA are up-regulated after orthotopic liver transplantation in tolerant rats: evidence for cytokine-mediated immune dysregulation.

BACKGROUND: Immune regulation requires antigen recognition, signaling, activation, secretion of cytokines, and effector function by lymphocytes. Although there is redundancy in the activation and function of the immune response, some cytokines simultaneously promote and suppress different pathways of immunity. In the experiments reported here we compare cytokine gene expression within liver allografts from tolerant rats with normal and isografted liver tissue. We also compare the secretion of interferon-gamma (IFN-gamma) in the supernatant from mixed lymphocyte cultures by using peripheral blood lymphocytes stimulated against donor antigen. METHODS: Orthotopic liver transplantations were performed using the cuff technique without hepatic artery revascularization. Nonisotopic in situ hybridization (ISH) was used to detect and localize messenger RNA to specific cells within tissue. Antisense DNA probes were generated to interleukin-2 (IL-2), IL-4, IL-10, and IFN-gamma. One-way mixed lymphocyte cultures were set up against irradiated donor splenocytes, and the supernatant was collected to measure IFN-gamma by enzyme-linked immunosorbent assay. RESULTS: Expression of IFN-gamma and IL-10 was up-regulated in tolerant animals versus normal or isografted liver (p = 0.0002 and 0.0001, IFN-gamma and IL-10, respectively). In situ hybridization localized the expression of messenger RNA predominantly to the cytoplasm of the hepatocytes. Levels of IFN-gamma were higher in the supernatant from proliferating peripheral lymphocytes against donor antigen from tolerant animals versus naive control animals. CONCLUSIONS: Expression of IFN-gamma and IL-10 is up-regulated in hepatocytes from allograft tissue after orthotopic liver transplantation. We believe that the up-regulation of IL-10 cross-regulates the effector function of IFN-gamma and supports cytokine-mediated immune dysregulation, which may be a mechanism of tolerance after orthotopic liver transplantation in rats.

Animals↗
PubMed1995

Assessment of living renal donors with spiral CT.

PURPOSE: To determine whether spiral computed tomography (CT) can be used to evaluate potential living renal donors. MATERIALS AND METHODS: Twelve potential living renal donors underwent spiral CT and conventional arteriography. CT angiography was performed with 30-second spiral acquisition during injection of 150 mL of nonionic iodinated contrast material into an antecubital vein at 5 mL/sec. Five minutes after injection, a frontal abdominal scout projection was obtained to assess the renal collecting system. Results of blinded interpretations of axial CT angiograms, three-dimensional CT angiograms, and conventional arteriograms were correlated with intraoperative findings in 11 cases. RESULTS: Axial and three-dimensional CT angiography were 100% sensitive for identifying seven accessory renal arteries and 14% and 93% sensitive for identifying five prehilar renal artery branches. Renal venous anomalies were confirmed in three patients at surgery. Operative management changed in four of 11 patients who underwent donor nephrectomy. CONCLUSION: Spiral CT holds promise as a single examination for anatomic assessment of living renal donors.

Adult↗
PubMed1995

Nurse-physician collaboration and decision outcomes in transplant ambulatory care settings.

OBJECTIVE: This study examined the nature of nurse-physician collaborative practice as reflected in problems presented by transplant patients in telephone contacts with clinical nurse specialists (CNSs). DESIGN: Exploratory descriptive study. SAMPLE/SETTING: The sample consisted of 202 renal and renal-pancreas transplant recipients who telephoned nurses at the outpatient clinic of a tertiary care medical center. METHODS: Over a period of 6 weeks, using a data collection form, nurse specialists recorded the types and frequencies of problems described by transplant patients via telephone interaction and categorized the outcomes of decisions. RESULTS: Of the 437 calls, averaging 2.16 calls per patient, problems were classified as general questions (46%), medication related (32%), and clinical signs and symptoms (22%) such as fever, rejection, colds, and urinary tract infections. Decision outcomes (n = 354) categorized as independent or collaborative for problem resolution were: CNS only (80%), MD only (11%), and collaborative (9%). CONCLUSIONS: Resolution of 80% of patients' problems presented in telephone interactions shows that advanced practice nurses play a pivotal role in the delivery of care to outpatient transplant recipients. Independent decision making on the part of the nurse occurs within the context of ongoing collaboration and communication with physician colleagues.

Adolescent↗