Biomedical subjects

D L Dunn

Publications and source records attributed to D L Dunn.

At least 181 records · Page 10Linked to original sources

PubMed1991

Treatment of invasive cytomegalovirus disease in solid organ transplant patients with ganciclovir.

The occurrence of cytomegalovirus infection after solid organ transplantation has been correlated with decrease patient and allograft survival. The disease has not been conquered for two majors reasons: the length of time to establish the diagnosis of CMV has been excessive, and suitable, nontoxic antiviral agents have not been available for use. The purpose of this study was to examine the current incidence and impact of tissue-invasive cytomegalovirus (TI-CMV) disease that developed in 93 patients who underwent solid organ transplantation at University of Minnesota Hospitals (3/1/87 and 6/30/89) and who were treated with antiviral agent ganciclovir ( [9-(1,3-dihydroxy-2-2-propoxymethyl)-guanine [DHPG]). During this same period of time 323 patients received kidney transplants and 71 received kidney-pancreas transplants. Three patient groups were defined: (1) no CMV; (2) CMV infection (cultural or serologic evidence of noninvasive CMV infection); and (3) evidence of TI-CMV disease based upon initial complaints of fever, malaise, dyspnea, or abdominal pain, leukopenia (WBC less than 3000/ml), and evidence of a positive CMV rapid antigen test, CMV culture, or the presence of characteristic CMV inclusion bodies upon examination of material obtained by means of bronchoscopy, upper-gastrointestinal endoscopy, colonoscopy, or liver or renal biopsy. Patients with solely fever, leukopenia, but without a rising CMV serum titer, or positive CMV urine or blood cultures were excluded from the study. A multivariate analysis revealed that rejection therapy, age greater than 50 years, and receiving an organ from a seropositive donor were all significant variables that predisposed to TI-CMV. Analysis of patient and kidney allograft survival indicated that asymptomatic CMV infection had little current impact upon patient or allograft survival, while patients who developed TI-CMV exhibited higher rates of allograft loss and mortality, despite DHPG therapy. Comparison with historical group of patients indicated that TI-CMV DHPG-treated patients exhibited a trend toward improved allograft survival that may be relevant because the historical group of patients included patients with mild CMV infection. DHPG therapy was well tolerated and produced minimal toxicity, and excellent 30-day cure rates (89.2%), although 21.2% of patients required retreatment subsequently. We are currently conducting a trial to compare the ability of DHPG administered plus an anti-CMV immune globulin preparation with acyclovir to prevent posttransplant TI-CMV disease.

Acyclovir↗

PubMed1991

Long-term outlook for renal transplant recipients with one-year function. "Doctor, what are my chances"?

Patients with renal transplants that survive the first year often ask about the chance of long-term function. We studied 1850 patients with primary transplants from June 7, 1963 to September 1, 1988 who had graft survival of greater than 1 year. Patients were grouped by donor type, diabetic status, and whether or not they received cyclosporine (CsA). Half-life (T1/2) was used to compare long-term survival rates. We determined the long-term graft survival inclusive and exclusive of death with function (DwF) in order to study all patients and to direct attention to immunologic losses. Pre-CsA, DwF was the major cause of graft loss in each cohort. Cause of DwF was cardiovascular (49%), infection (26%), and cancer (14%). The percentage of patients experiencing DwF was much higher in the pre-CsA group vs. the CsA group: HLA-identical living related donor, 16% vs. 3%; non-HLA-identical LRD, 22% vs. 5%; and cadaver donors, 26% vs. 11%. T1/2 for 711 transplants to diabetics (DM) was 9.01 +/- .54 years, while for transplants to 1139 nondiabetics (NDM) T1/2 was 13.57 +/- .68 (P less than .05). When DwF is excluded (DwFex) DM T1/2 = 23.5 +/- 2.69 and NDM T1/2 = 22.2 +/- 1.55 (NS). Overall, for HLA-identical transplants (n = 297) T1/2 = 26.13 +/- 3.35 and DwFex T1/2 = 104.3 +/- 28.93. Nonidentical LRD (n = 845) T1/2 = 11.25 +/- .61 and DwFex T1/2 = 19.37 +/- 1.55. For CAD (n = 701) T1/2 = 9.10 +/- .54 and DwFex T1/2 = 17.49 +/- 1.65. Comparing pre- and post-CsA cohorts, CsA has not resulted in significant improvement in long-term graft survival by T1/2 analysis with DwFex. It appears that overall long-term graft survival has improved with the introduction of CsA. Much of the improvement may be attributed to better first year graft survival and a reduction in cases of DwF. DM patients have an equal opportunity for long-term graft survival if they do not die from other causes. Excluding DwF, especially as an older population is transplanted, is important in determining chances of immunologic loss. Use of this type of analysis suggests that long-term outlook for 1-year graft survivors is excellent.

Cyclosporins↗

PubMed1991

Evidence that combined procurement of pancreas and liver grafts does not affect transplant outcome.

We compared outcome after pancreas and liver transplantation when both organs were retrieved from the same donor to outcome when only one or the other organ was retrieved. A total of 166 cadaver pancreata were transplanted at our institution between November 1984 and August 1989; 64 were obtained from donors in whom the liver was also donated (LD), and 102 were retrieved from non-liver donors (non-LD). Of the 64 LD pancreata, 53 were the entire organ with a segment of duodenum and 11 were segmental. Both the superior mesenteric artery (SMA) and celiac axis (CA) were retained with the pancreas in 13, while in 40 pancreata the CA was retrieved with the liver and the blood supply to the pancreas was reconstructed [end-to-side anastomosis of splenic artery (SA) to SMA in 11 and a Y-graft of donor iliac bifurcation to SA and SMA in 29]; a graft of common iliac vein was used to extend the portal vein in 10. The technical failure rate was 8/64 (12%) in LD pancreata, and 13/102 (13%) in non-LD pancreata (P greater than 0.1). The overall pancreas allograft survival rate at 1 year was 76% for pancreata obtained from LD (n = 64) and 64% for technically successful transplanted pancreata obtained from non-LD (n = 102, P greater than 0.1). One-year actuarial patient survival was 95% in the LD group and 90% in the non-LD group (P greater than 0.1). Among the 64 livers from pancreas donors (PD), 20 were transplanted at our hospital, 42 were transported to other institutions, and 2 were not transplanted. Follow-up information regarding 47 primary orthotopic adult, whole liver PD recipients (18 at our hospital, 29 at other institutions) was available for analysis and was compared with information concerning 62 adult recipients of primary orthotopic whole livers from non-PD transplanted during the same period at our institution. The total PNF rate among 47 PD liver allografts was 2/47 (4%), compared with 1/62 (1%) for the livers from non-PD (P greater than 0.1). The technical failure rate for the PD group was 1/47 (2%) versus 5/62 (8%) in the non-PD group (P greater than 0.1). The overall liver allograft survival rate at 1 year was 75% for livers obtained from PD (n = 47) and 81% for livers obtained from non-PD (n = 62, P greater than 0.1). One-year actuarial patient survival was 88% in the PD group and 81% in the non-PD group (P greater than 0.1). We concluded that simultaneous procurement of liver and pancreas grafts had no significant detrimental effect on the rate of technical failure, or on allograft or patient survival after either pancreas or liver transplantation.

Adult↗

PubMed1991

Pancreas retransplants compared with primary transplants.

The improved results with pancreas transplantation in general, and the emerging evidence that the procedure favorably influences the course of secondary diabetic complications, given an impetus to retransplant patients whose initial graft has failed. In order to determine whether a pancreas retransplant policy is justified, we analyzed the results at our own institution. From 1978 through 1989, 327 pancreas transplants were performed in 261 patients, including 259 primary (79%) and 68 retransplants (21%) after a previous one failed (including 2 primary transplants performed elsewhere), with 48 second (15%), 18 third (5%), and 2 fourth (1%) transplants. The surgical techniques used in the 261 primary PxTxs were open-duct free drainage into the peritoneal cavity in 15 recipients, of whom 3 (20%) were retransplanted: duct occlusion in 34, of whom 9 (26%) were retransplanted intestinal drainage in 78, of whom 23 (29%) were retransplanted; and bladder drainage in 134, of whom 13 (10%) were retransplanted. The surgical techniques used for the 68 pancreas retransplants were duct occlusion in 11 (10 second, 1 third), intestinal drainage in 12 (9 second, 3 third), and bladder drainage in 45 (29 second, 14 third, and 2 forth); bladder drainage has been used nearly exclusively for the most recent pancreas retransplants. The recipient categories in the 261 primary transplants were pancreas alone in 115, of whom 29 (25%) were retransplanted, pancreas after kidney in 81, of whom 17 (21%) were retransplanted, and simultaneous pancreas and kidney transplants in 63, of whom 2 (3%) were retransplanted. Of the 68 pancreas retransplants, 32 (47%) were pancreas alone (26 second, 6 third), 24 (35%) were pancreas after kidney (17 second, 6 third, 1 fourth), and 12 (18%) were simultaneous pancreas and kidney (5 second, 6 third, 1 fourth). Overall patient survival rates were similar (P = 0.48), at 1 month (actual [98% after primary and 94% after retransplantation]) and at 1 year (actuarial [91% vs. 89%]). Overall graft functional rates were also similar, at 1 month (actual [76% for all primary and 79% for all retransplants - P = 0.9]), and at 1 year (actuarial [46% vs. 43% - P = 0.9]). Causes of graft losses at 1 months were similar for primary (18% were technical failures, 6% were rejected) and retransplant (16% were technical failures, 3% were rejected) cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1991

Long-term metabolic function of pancreas transplants and influence of rejection episodes.

Pancreas grafts, when not rejected, can sustain an insulin-independent state in type I diabetic recipients for indefinite periods. To what extent the metabolic control achieved approaches that of normal individuals, the relationships between graft endocrine and exocrine function, the effect of reversible rejection episodes on subsequent graft function, and the correlation between the results of serial tests of graft function were determined by studies at 1 month, 1 year, and 2 years in a cohort of 39 recipients (29 females, 10 males; mean age (+/- SD), 33 +/- 5 years; mean duration of diabetes, 22 +/- 6 years) of bladder-drained pancreas transplants performed between November 1984 and December 1988. Fifteen patients received a pancreas transplant alone, 8 a pancreas after a kidney, and 16 a simultaneous pancreas/kidney transplant. Graft endocrine function was tested by a 24-hr metabolic profile of blood glucose levels before meals, at 1 and 2 hr after meals, and during the night (14 values in all), by intravenous and oral blood glucose tolerance tests, and by glycosylated hemoglobin levels (HA1 and HA1c). Graft exocrine function was assessed by urine amylase activity (U/hr). The results of the tests in the recipients were subjected to paired comparisons between timepoints and at each timepoint to the results of the same tests in 55 normal nondiabetic control individuals. The means of the mean 24-hr profile glucose (mg/dl) values were significantly lower (P less than 0.05) at 1 and 2 years posttransplant (116 +/- 27 and 115 +/- 15, respectively) than at 1 month (128 +/- 31) in the recipients, but the mean of the mean values in the normal controls (100 +/- 7) was even lower (P less than 0.05). Mean values of individual timepoints during the profile were significantly lower for 6 of the 14 values in the controls than in the recipients. The mean IVGTT K value of the normal controls (-1.9 +/- 0.4%) was significantly lower than the 1-month and 2-year values of the recipients (-1.5 +/- 0.5% and -1.3 +/- 0.6%, respectively), but the comparison with the 1-year value (-1.6 +/- 0.6%) was not significant. The mean glucose levels at zero minutes and between 120 and 300 min of the OGTTs were significantly lower at both 1 and 2 years than at 1 month in the recipients, and the values in the control group were also significantly lower than in the recipients at 1 month but not at 1 and 2 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗

PubMed1991

Assessment of renal function in type I diabetic patients after kidney, pancreas, or combined kidney-pancreas transplantation.

The long-term kidney function (KF) in the three categories of diabetic type 1 pancreas (P) transplant recipients (simultaneous P and kidney [SPK]; P after K [PAK]; PTx alone [PTA] was studied sequentially over a 2-year period in 62 patients who received a bladder-drained allograft that functioned for at least 1 year. Fifty-three (85%) patients were analyzed at 1 month, 42 (68%) at 1 year, and 16 (26%) at 2 years posttransplant. Comparison of KF was made within each recipient category and between categories. In addition, the KF in the SPK and PAK patients was compared to a matched group of diabetic type 1 recipients of KTx alone (functioning at least 1 year). In the SPK group, KF was stable over time: the mean +/- SD serum creatinine (mg/dl) was 1.5 +/- 0.5 at 1 month, 1.8 +/- 1.0 at 1 year, and 1.7 +/- 0.5 at 2 years. In the PAK category, the pre-PTx serum creatinine value was 1.4 +/- 0.5, and then remained stable after the PTx (1.3 +/- 0.2 at 1 month, 1.3 +/- 0.4 at 1 year, and 1.2 +/- 0.4 at 2 years). In the recipients of a PTA, the values at 1 month (1.1 +/- 0.4), 1 year (1.4 +/- 0.5), and 2 years (1.3 +/- 0.5) were significantly higher (P less than or equal to 0.03) than the pre-PTx value (0.9 +/- 0.2); and results at 1 month and 2 years were lower than those at 1 year, a significant difference compared to the 1-month value (P = 0.01). Comparisons between the categories of PTx recipients demonstrated that the pre-PTx value in the PTA group (0.9 +/- 0.2) was significantly lower (P = 0.01) than in the PAK group (1.4 +/- 0.5). At 1 month the serum creatinine value in the PTA category (1.1 +/- 0.4) was significantly lower (P = 0.02) than in the SPK category (1.5 +/- 0.5), but thereafter (1 and 2 years) the difference was not significant (P greater than 0.1). KF in recipients of KTx alone was similar at each post-Tx time point when compared to the SPK and PAK categories. We concluded that a PTx can be performed in diabetics without a detrimental effect on a simultaneously or a previously transplanted kidney and that a statistically significant, albeit minimal to moderate, initial but not progressive deterioration in native KF occurs in recipients of a PTx alone.

Creatinine↗

PubMed1991

Pharmacologic basis for high-dose oral acyclovir prophylaxis of cytomegalovirus disease in renal allograft recipients.

The incidence of cytomegalovirus disease, the most important infectious complication of renal transplantation, was reduced in renal allograft recipients by a regimen of prophylactic high-dose oral acyclovir. To analyze the pharmacologic aspects of our prophylactic approach, we evaluated safety, pharmacodynamics, and in vitro susceptibility data. One hundred four recipients of cadaveric renal allografts received either oral acyclovir (n = 53) in doses of up to 3,200 mg/day or a placebo (n = 51) for 12 weeks posttransplant. Leukocyte count and serum creatinine were selected as markers of laboratory safety and were evaluated pretransplant, at study midpoint (creatinine only), and at study completion. Concentrations of acyclovir in plasma were determined to verify the ability of the dosing strategy to achieve predicted values. Viral resistance was assessed by calculation of in vitro 50% inhibitory concentrations (IC50s) of acyclovir for the cytomegalovirus strains collected from the subjects. Our results showed no difference in leukocyte count or serum creatinine between the acyclovir and placebo recipients. Plasma acyclovir concentrations were maintained within the expected limits and did not differ between patients who developed cytomegalovirus disease and those who did not. The mean acyclovir IC50s for cytomegalovirus isolates were 42.6 mumol/liter in the acyclovir recipients and 48 mumol/liter in the placebo recipients. We conclude that the clinical benefit of high-dose oral acyclovir therapy occurred despite plasma drug concentrations below the mean IC50 for the patient viral isolates. Furthermore, the use of the regimen did not produce leukopenia, adversely affect renal function, or alter the susceptibility of cytomegalovirus strains to acyclovir. This approach and dose adjustment scheme may be appropriate for other immunocompromised patients at risk for cytomegalovirus infection and disease.

Acyclovir↗

PubMed1991