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Biomedical subjects

D L Dunn

Publications and source records attributed to D L Dunn.

At least 91 records · Page 5Linked to original sources
PubMed1994

Recipient risk factors have an impact on technical failure and patient and graft survival rates in bladder-drained pancreas transplants.

Recipient selection criteria for pancreas (Px) transplantation differ among centers, based on perceived recipient risk factors, and their validity has not been determined. At the University of Minnesota we have been very liberal in accepting patients for Tx, some of whom have risk factors cited as exclusion criteria by other centers, giving us the opportunity to determine, retrospectively, the impact of their presence on outcome. Between July 1986 and March 1993, we performed 319 bladder-drained cadaver Px Txs at the University of Minnesota, 166 simultaneous with a kidney (SPK), 68 after a kidney (PAK), and 85 alone (PTA). To determine which putative "risk factors" influence patient and graft survival, we used uni- and multivariate (Cox regression) analyses to assess the impact of recipient category, duration of diabetes, and age at onset and at Tx; presence of pre-Tx cardiac (CD) disease (myocardial infarction, bypass, angioplasty), peripheral vascular disease (PVD) (stroke, bypass, angioplasty, amputation); blindness, hypertension, and excess weight; and of Px re-Txs. The incidences of all risk factors except re-Tx were significantly higher in SPK than PTA recipients. Px re-Txs comprised 40% of PAK, 26% of PTA, and 10% of SPK cases (P < 0.0001). Duration of diabetes correlated (P < or = 0.01) with all risk factors but one (hypertension). Recipient age correlated (P < or = 0.01) with CD, blindness, duration of diabetes, and age at onset of diabetes; CD risk factors correlated (P < 0.015) with hypertension and PVD. Recipient age (> or = 45) influenced the technical failure rate only in SPK recipients, with a relative risk (RR) of 2.13 (P = 0.08). Recipient age influenced Px graft and patient survival rates in both SPK and PAK recipients; for those > or = 45, the RR of graft loss was 1.73 and 1.76, respectively (P < or = 0.25), and the RR for ultimately dying was 3.07 in PAK (P = 0.02) and 5.86 in SPK (P = 0.17) recipients. SPK recipients with CD factors were at higher risk to ultimately die (RR = 3.78, P = 0.009), independent of age. Px re-Txs were not at higher risk to fail in PTA, but were in PAK recipients (RR = 1.86, P = 0.09); the risk for technical failure was higher for re-Txs only in SPK recipients (RR = 2.11, P = 0.24). Blindness, hypertension, PVD, and duration of diabetes did not negatively influence patient and graft outcome in any recipient category.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation.

Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n = 133; GCV+HIg, n = 133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n = 28, 21.0%) in the ACV group, while significantly more patients (n = 42, 31.6%) in the GCV + HIg group developed group developed CMV disease slightly later (2.83 +/- 0.70 months) than those who received GCV/HIg (2.15 +/- 0.21 months, P > 0.01). Multivariate analysis demonstrated (2.15 +/- 0.21 months, P > 0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P < 0.001), while the difference between ACV versus GCV + HIg prophylaxis was also significant (P = 0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV + HIg prophylaxis is used in this patient population.

Acyclovir↗
PubMed1994

Successful long-term outcome with 0-haplotype-matched living-related kidney donors.

The waiting list for cadaver kidney transplantation continues to grow. Yet there has been little increase in the number of living-donor transplants. At many centers, willing relatives are turned down as potential donors because of poor HLA ABDR matching with the recipient. It has been our policy to accept the 0-haplotype-match (0-HTM) living-related donor. We studied long-term (6-year) outcome of 0-HTM transplants compared with the outcome of transplants from 1- and 2-HTM recipients and from cadaver donors. Since 1984, 352 adults have received primary living-related renal transplants, and had a minimum of 1 year of follow-up: 92 2-HTM, 216 1-HTM, and 44 0-HTM. In the same period and with the same follow-up, 362 adults have received primary cadaver (CAD) renal transplants. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone (triple therapy) for living-donor and sequential therapy for CAD recipients. ABDR match (mean +/- SD) for 0 HTM was 1.3 +/- 8; CAD, 2.0 +/- 1.6; % peak panel-reactive antibodies (PRA) for 0 HTM was 1.2 +/- 5.3; 1 HTM, 6.7 +/- 20; 2 HTM, 7.5 +/- 21; CAD, 15.5 +/- 30. The percentage of PRA at the time of transplant for 0 HTM was .7 +/- 4.4; 1 HTM, 4.1 +/- 1.6; 2 HTM, 6 +/- 18; CAD, 7.2 +/- 20. While the number of ABDR matches was significantly fewer for 0 HTM than for the other groups, the % PRA at transplant and the peak % PRA were less in the 0-HTM group. Other demographics were not significantly different. Patient survival was significantly lower in the CAD group vs. 2-HTM recipients (P < .05). The living-related grafts had significantly greater survival than the CAD grafts (P < .05), but there was no significant difference between 0-, 1-, and 2-HTM graft survival. The most common causes of graft loss in all groups were death and chronic rejection. In our experience, the long-term graft survivals of 0-HTM and 1-HTM transplants are the same, and both are superior to CAD results, using 0-HTM living-related donor transplants should be continued and encouraged.

Adult↗
PubMed1994

Inhibition of splenic macrophage tumor necrosis factor alpha secretion in vivo by antilipopolysaccharide monoclonal antibodies.

OBJECTIVE: This study tried to determine whether administration of antilipopolysaccharide (LPS) murine monoclonal antibody (mAb) 2A3 to mice was associated with (1) protective capacity during experimental gram-negative bacterial sepsis, and (2) inhibition of tumor necrosis factor alpha (TNF-alpha) secretion in the systemic circulation and at the tissue level during experimental infection. DESIGN: Mice received an initial intravenous injection of either saline or 100 micrograms of anti-LPS mAb 2A3, and 1 hour later underwent intraperitoneal inoculation of viable Escherichia coli 0111:B4. Mortality was assessed daily for 7 days. Separate groups of mice were treated similarly and plasma TNF-alpha concentrations were determined from blood samples obtained at 1, 3, 6, 10, and 16 hours after infection by enzyme-linked immunosorbent assay. Concurrently, splenocytes harvested from animals 3, 10, and 16 hours after infection were incubated in culture ex vivo and supernatant TNF-alpha levels were determined. RESULTS: Pretreatment with anti-LPS mAb 2A3 prior to an intraperitoneal challenge of live E coli 0111:B4 was associated with the following: (1) significant protective capacity (100% vs 0% mortality, P < .001); (2) inhibition of plasma TNF-alpha levels 16 hours after infection (1257 +/- 323 pg/mL vs 292 +/- 254 pg/mL, P < .001); and (3) abrogation of TNF-alpha secretion derived from splenic macrophages isolated 16 hours after bacterial challenge (229 +/- 12 pg/mL vs 107 +/- 48 pg/mL, P < .05). CONCLUSIONS: These results strongly support the contention that inhibition of LPS-induced TNF-alpha secretion at both the tissue and systemic levels is a key mechanism by which anti-LPS mAbs provide protection during gram-negative bacterial peritonitis. We believe that in vivo monitoring of macrophage cytokine secretion will be critical for elucidating the precise role of a variety of mediators in the pathogenesis of gram-negative bacterial sepsis.

Animals↗
PubMed1994

Characterization and impact of wound infection after pancreas transplantation.

OBJECTIVE: To characterize the incidence, microbial pathogenesis, risk factors, and impact of wound infection after pancreas transplantation. DESIGN: Retrospective analysis. SETTING: A large university hospital. PATIENTS: From January 1, 1990, to September 30, 1993, 197 patients underwent 207 consecutive pancreas transplantation procedures. MAIN OUTCOME MEASURES: Wound infection and patient and allograft survival rates at 1 year. RESULTS: Sixty-nine patients (33%) suffered wound infections: 21 (10%) were superficial; 31 (15%), deep; and 17 (8%), combined. Most (74%) wound infections were monomicrobial. Staphylococcus epidermidis and Candida species were the most common pathogens. Prolonged operating time, older donors, and enteric drainage were associated with higher wound infection rates. Deep and combined wound infections led to allograft loss despite subsequent salvage procedures. Combined wound infection was associated with significantly higher mortality. CONCLUSIONS: A deep wound infection should be an indication for allograft removal. Antifungal prophylaxis, stringent donor criteria, and delayed primary wound closure should lower the incidence of wound infection.

Adult↗
PubMed1994

Clinical characteristics of post-transplant lymphoproliferative disorders.

PURPOSE: To study the histopathologic findings, clinical course, and therapeutic outcome of patients who developed a lymphoproliferative disorder after undergoing solid organ transplantation. PATIENTS AND METHODS: A series of 26 patients who developed a lymphoproliferative disorder after solid organ transplant during a 27-year period were studied. RESULTS: The 26 patients ranged in age from 6 to 68 years (median 42 years). The lymphoproliferative disorder was diagnosed from 1 to 211 months (median 80 months) after transplantation. The type of transplant was kidney (n = 21), heart or heart-lung (n = 4), or liver (n = 1). Most patients received azathioprine and prednisone, in addition to antilymphocyte globulin or cyclosporine, for post-transplant immunosuppression. Eight patients had lymphoma that could be classified according to the International Working Formulation (IWF-F, IWF-G, IWF-H). Sixteen patients had polymorphic lymphoma, and 2 patients were classified as having polymorphic lymphoid hyperplasia. Patients were staged by the Ann Arbor staging system. Nine patients had stage I disease, 4 stage II, 6 stage III, and 7 stage IV. Central nervous system, lung, or marrow involvement was present in 27%, 23%, and 14% of patients, respectively. In the 17 patients studied, immunophenotype was monoclonal B-cell (n = 12), malignant T-cell (n = 2), or polyclonal B-cell (n = 3). The initial therapeutic approach was generally a reduction in immunosuppression, but, thereafter, the approach to therapy varied. In patients with localized disease, surgical excision and/or involved field radiotherapy were utilized as applicable. For patients with more extensive disease, other approaches such as high-dose acyclovir, combination chemotherapy, or alpha interferon were utilized. Overall, 15 of 26 patients (58%) responded to systemic therapy or were rendered disease-free either by surgery or radiation, including 8 (31%) with a complete remission (CR). Only 3 of 9 patients responded to chemotherapy, whereas 4 of 13 patients responded to acyclovir (including 3 patients who experienced CR). Remission duration ranged from 8 to 122 months (median 32+ months). Twenty-one of 26 patients (81%) have died. Survival ranged from less than 1 to 122 months (median 14 months). CONCLUSION: The outcome of patients with post-solid organ transplant lymphoproliferative disorders is poor, and the optimal approach to therapy is not clear. Newer therapeutic approaches are thus needed to improve the outcome of these patients.

Adolescent↗
PubMed1994

Diagnosis and treatment of cytomegalovirus disease in pediatric renal transplant recipients.

The purpose of this study was to identify factors associated with the development of cytomegalovirus (CMV) disease and to assess the morbidity of this illness in pediatric renal transplant patients. The authors retrospectively reviewed the records of 135 patients (< 18 years of age) who underwent a total of 151 transplants (146 kidney transplants, five kidney/liver transplants) over 5 years (average follow-up period, 33.0 +/- 21.7 months). They assessed the risk factors that previously have been associated with the development of CMV disease in adults (age, occurrence of acute rejection episodes, and preoperative donor and recipient CMV serological status) and evaluated the incidence of associated graft loss and mortality. Twenty-two episodes of CMV disease were diagnosed based on evidence of CMV infection and on clinical symptoms; the episodes were treated in 17 patients. A multivariate analysis showed that the development of CMV disease was associated with age of > or = 13 years (P = .02), concomitant liver transplantation (P = .01), and treatment of acute rejection (P = .04). In addition, patients who were CMV-seronegative preoperatively and received a graft from a CMV-seropositive donor (P = .04) or who were CMV-seropositive preoperatively and received a graft from a CMV-seronegative donor (P = .02) were more likely to have CMV disease. Although all patients with CMV disease required hospitalization and were treated with intravenous ganciclovir, CMV disease was not associated with increased allograft loss or mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Complications of ureterovesical anastomosis in kidney transplant patients: the Minnesota experience.

We reviewed urologic complications of 1183 consecutive primary or secondary renal transplants performed with bladder anastomoses at the University of Minnesota Hospital between 1985 and 1993. The Politano-Leadbetter (PL) technique of ureteroneocystostomy was used in 410 patients; the multistich (MS) extravesical technique modified from the methods of Witzel, Sampson, and Lich in 295; and the extravesical single-stitch (SS) technique in 478. Urologic complications occurred in 81 patients (6.8%). Of these complications, 68 (5.7%) were early (< 4 months) and 13 (1.1%) late; 32 (7.8%) were after PL, 17 (5.8%) after MS, and 32 (6.7%) after SS. A total of 13 patients had an anastomotic leak, 7 (1.7%) after PL, 4 (1.4%) after MS, and 2 (0.0004%) after SS; 49 patients had a ureterovesical obstruction, 16 (4.0%) after PL, 12 (4.0%) after MS, and 21 (4.2%) after SS; 5 patients had a ureteropelvic obstruction, 2 (0.5%) after PL, 2 (0.7%) after MS, and 1 (0.2%) after SS; and 14 patients had hematuria, 7 (1.7%) after PL, 1 (0.34%) after MS, and 6 (1.3%) after SS. Of the 81 patients with urologic complications, one (1%) resolved spontaneously; 30 (37%) were treated with temporary percutaneous nephrostomy, 17 (21%) with dilatation and stent; the 14 (17.3%) with hematuria were treated via cystoscopy; 19 (23%) required reoperation. Only 2 (2.5%) patients lost their graft. For both cadaver and living donor recipients, there was no difference between techniques for early and late complications of leakage, stricture, and hematuria. Each technique has certain advantages and each should be in every surgeon's repertoire.

Anastomosis, Surgical↗
PubMed1994

De novo cancer in cyclosporine-treated and non-cyclosporine-treated adult primary renal allograft recipients.

We compared the incidence of de novo tumors developing in 1165 primary adult renal allograft recipients treated with azathioprine (AZA)-prednisone (Pred)-antilymphocyte globulin (ALG) (CONV group) with that in 722 patients receiving cyclosporine (CSA) as part of double (CSA-Pred), triple (CSA-Pred-AZA), or quadruple-therapy (CSA-Pred-AZA-ALG) protocols. Mean +/- SD follow-up was 9.5 +/- 6.4 years for the CONV group and 6.2 +/- 2.7 years for the CSA group. Overall, 124 patients (10.6%) in the CONV group and 34 patients (4.7%) in the CSA group developed malignancies, with nonmelanoma skin cancers and lymphomas comprising 55% and 13% of cancers in the CONV group and 65% and 3% of cancers in the CSA group, respectively. There were no significant differences in overall cancer (p = 0.41) or skin cancer (p = 0.97) incidence between non-CSA-treated and CSA-treated patients by Kaplan-Meier life-table analysis; however, CONV-treated patients demonstrated a higher incidence of lymphoma (p = 0.05). The mean (+/- SD) time to overall and skin cancer occurrence was significantly shorter in the CSA group: 37 +/- 22 versus 90 +/- 52 months (p < 0.001) and 40 +/- 24 versus 92 +/- 52 months, respectively. When the Cox Proportional Hazard Model was utilized to assess the relative importance of age, diabetic status, donor source, sex, and immunosuppressive regimen in determining cancer development, age > or = 50 years and nondiabetic status were significant independent prognostic indicators, while immunosuppressive regimen was not. Graft and patient survival were significantly greater in CONV-treated patients developing cancer than in those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Kidney transplant outcome with and without right renal vein extension.

Use of the vena cava to extend the right renal vein for cadaver transplantation is controversial. Right renal vein extension permits an easier anastomosis and possibly better positioning of the kidney, but may create a low flow or turbulent state. We studied whether use of a vein extension had an impact on outcome. Between January 1986 and April 1993, 305 cadaver transplant recipients received a right kidney. Of these, 76 received a graft with vein extension. None of the 76 experienced technical vascular complications versus 5 of the 229 (2.2%) without vein extension. There was no difference in 1- and 2-year graft survival for those with versus without extension. We conclude that there is no increased risk with use of the vena cava extension and recommend that the donor team routinely provide the right kidney with the vena cava attached. This allows the recipient team to determine whether an extension is appropriate for the particular recipient.

Anastomosis, Surgical↗