PubMed Health⌕ Search

Biomedical subjects

D C Dafoe

Publications and source records attributed to D C Dafoe.

At least 37 records · Page 2Linked to original sources
PubMed1997

Eradication of cytomegalovirus reactivation disease using high-dose acyclovir and targeted intravenous ganciclovir in kidney and kidney/pancreas transplantation.

BACKGROUND: The attack rate of cytomegalovirus (CMV) is over 50% in solid organ transplant recipients at risk for primary CMV infection and in those receiving antilymphocyte antibody therapy. Various CMV prophylaxis regimens over the last few years have reduced the attack rate to around 20% overall. METHODS: We report our results using high-dose acyclovir for 3 months after transplant, with targeted intravenous ganciclovir for the duration of any antilymphocyte antibody therapy, in our kidney and simultaneous pancreas/kidney transplant recipients. Records of 109 consecutive patients over a 2-year period were reviewed. RESULTS: Six cases of CMV disease were identified. Five cases occurred in 21 patients at risk for primary CMV disease (24%), whereas only one case occurred in 73 patients at risk for CMV reactivation (1.4%). CONCLUSION: We conclude that high-dose acyclovir and targeted ganciclovir is excellent prophylaxis against CMV reactivation in kidney and simultaneous pancreas/kidney transplantation.

Acyclovir↗
PubMed1997

Insulin-like growth factor-I ameliorates delayed kidney graft function and the acute nephrotoxic effects of cyclosporine.

BACKGROUND: Delayed graft function (DGF) is a relatively common complication after cadaveric renal transplantation. The adverse effect of DGF on long-term graft survival has lead to intensive efforts to reduce ischemic graft injury. In this study we examined the effects of a new protective treatment based on insulin growth factor (IGF)-I. We evaluated the impact of the treatment on renal recovery and on the nephrotoxicity that is a common side effect of mainstream immunosuppressants. Because therapy with IGF-I or the analog des(1-3)IGF-I is effective in treating experimental ischemic renal failure, these peptides may be useful as perspective clinical treatments. METHODS: We have addressed three areas relating to the potential use of IGF-I and its analog des(1-3)IGF-I. First, because of the immunogenic properties of IGF-I, we assessed the effect of des(1-3)IGF-I on the rejection of skin allografts in Lewis rats. Next we determined whether treatment with des(1-3)IGF-I influences the early function of transplanted kidneys in a model of DGF induced by a combination of warm and cold ischemia. Finally we tested whether IGF-I protects against acute cyclosporine nephrotoxicity. RESULTS: Des(1-3)IGF-I did not accelerate the rejection of the skin grafts (P=0.57). The administration of this peptide in a model of syngenic renal transplant improved the early function of the graft. Postoperative values of creatinine and blood urea nitrogen were significantly better (P<0.05) in treated animals. IGF-I also ameliorated the nephrotoxicity of cyclosporine, with better values of creatinine and blood urea nitrogen (P<0.05). CONCLUSIONS: In evaluating this study it should be recognized that the animal models studied, although widely used, differ from the human condition. However, IGF-I and des(1-3)IGF-I exhibit properties that strongly suggest their value in preventing clinical DGF, and they deserve further studies.

Animals↗
PubMed1997

Regimens of IGF-I treatment in fetal pancreas transplantation.

Transplantation of fetal pancreas (FP) is a potential treatment for diabetes mellitus. FP has remarkable proliferative capacity and may be induced to expand sufficiently to provide a functional beta cell mass in adult recipients. We have demonstrated that local delivery of recombinant insulin-like growth factor-I (IGF-I) onto FP isografts is sufficient to reverse streptozotocin-induced diabetes in animals receiving as few as 4 fetal pancreata. In this current study we investigated other regimens of IGF-I delivery in an attempt to define whether its effects on FP required local delivery or whether other, more clinically feasible, forms of treatment would suffice. In our model, diabetic Lewis rats received isografts of 16 FP into the anterior thigh intramuscular (IM) site. In the group of FP recipients treated with vehicle alone, no animals converted to euglycemia (0/8). When the IM site was pretreated locally with 14 days of continuous IGF-I administration (69 micrograms/kg per day) prior to FP transplantation, 100% of the recipients (10/10) became euglycemic with a mean interval from transplant to euglycemia of 35 +/- 15 days (P < 0.001 when compared to vehicle alone). No significant advantage over the vehicle alone group was gained either when the FP tissue was cultured for 48 hr in the presence of IGF-I (100 micrograms/ml) and then implanted (27% conversion to euglycemia, 3/11) or when FP isografts were treated with continuous subcutaneous delivery of IGF-I (69 micrograms/kg per day over 14 days) distant from the transplant site (0% conversion to euglycemia, 0/6). IGF-I increased the rate of conversion to euglycemia either when delivered locally to FP isografts or when delivered to the transplant bed prior to transplantation. This suggests an active role of the IGF-I-treated transplant bed in the success of FP transplantation.

Animals↗
PubMed1997

Bladder augmentation can be problematic with renal failure and transplantation.

Ten consecutive patients with failure of urinary bladder augmentation (UBA) performed either prior to or after reaching end-stage renal disease (ESRD) were studied. Seven patients developed increased hydroureteronephrosis, infectious complications, and advanced to ESRD after UBA. The mean time to development of ESRD in patients who had UBA performed with moderate chronic renal failure (CRF) was 1.8 years. The UBAs in all seven patients were taken down prior to transplantation. Subsequently, five of these UBA-takedown patients have received kidney grafts and all have stable, good renal function. Three patients had their UBA performed after they reached ESRD, in preparation for renal transplantation. All three of these patients experienced recurrent urosepsis following transplantation, resulting in death in one patient and loss of graft in another. The third patient will undergo takedown of the UBA. This study suggests that UBA may possibly not be the best option for patients with moderate CRF and those awaiting transplantation.

Adolescent↗
PubMed1997

Kidney and kidney/pancreas transplantation at Stanford University Medical Center.

The disparity between the supply of cadaveric donors and the demand for renal allografts continues to grow. We have taken a multifaceted approach to increase the allograft pool: 1. Spiral computed tomography to evaluate potential living kidney donors is safer, less invasive, less expensive and more time efficient and thus should encourage living organ donation. 2. Use of selected expanded criteria cadaveric donor kidneys (aged 60 or over, hypertensive) in size- and age-matched recipients have short-term function at 3 and 6 months comparable to standard cadaveric renal allografts. 3. Kidneys from expanded criteria donors over age 59 and with an adjusted creatinine clearance less than 90 ml/min should be used as a dual kidney transplant into an appropriate sized- and aged-matched recipient. 4. Kidneys from pediatric donors < 5 years of age should be utilized as en-bloc grafts, when transplanted into adult recipients. Pediatric renal transplantation poses numerous challenges given the different and problematic etiologies of ESRD, the surgical considerations in small children and infants and the enhanced immune response witnessed in children. Nevertheless, renal transplantation is clearly the therapy of choice for children with ESRD and excellent results can be obtained through strict adherence to surgical detail, tight immunosuppressive management, and aggressive fluid management in infants and small children. We feel it is also critically important that transplantation and follow-up care be carried out by an integrated and experienced surgical and medical team. Managed healthcare has had profound effects on the practice and management of transplantation centers. The one area of greatest impact has been the pressure upon programs to reduce their cost of transplantation. We have initiated a number of new outpatient treatment protocols as part of an effort to contain costs. Most patients with acute rejection are evaluated (including transplant kidney biopsy) and treated in an ambulatory setting. Completion of OKT3 therapy in selected patients is also performed at home through visiting nurses or at our ambulatory care center. Additionally, treatment of CMV disease is now performed almost exclusively on an outpatient basis.

Actuarial Analysis↗
PubMed1996

The kidneys that nobody wanted: support for the utilization of expanded criteria donors.

The continuing shortage of cadaveric donors necessitates constant reappraisal of donor refusal criteria. From 1/1/95 to 3/20/96, 180 renal transplants were performed at our center. Of these, 26 were kidney/pancreas, 30 pediatric, 37 live donor adult, and 87 adult cadaveric renal transplants (CRT). In the CRT group there were 31 recipients of kidneys that all other local transplant centers declined. We retrospectively compared this group of kidneys that nobody wanted (KNW) to the remaining 56 CRTs (controls) performed at our center during the same period. Of the 31 recipients of KNW, 18 received kidneys declined for reasons of advanced age, defined as > or =60 years (including 8 who also had a history of hypertension, 4 who also had >10% sclerosed glomeruli on biopsy, and 3 also declined based upon donor quality because of acute injury), 8 for donor quality alone (e.g., prolonged hypotension), 3 on the basis of biopsy results alone, and 2 for anatomic abnormalities. Twelve recipients of KNW were "dual transplanted" with both donor kidneys. Of 27 donor variables compared between the KNW and control groups, only donor age (52+/-17 versus 40+/-17 years, respectively) and lowest total 4-hr urine output (327+/-208 versus 507+/-437 cc, respectively) proved to be significantly different (p< or =0.05). Of the 25 recipient variables examined, a significant difference was found only in serum creatinine at one month posttransplant (2.6+/-1.8 versus 1.8+/-1.0 mg/dl, respectively), although there was no difference in serum creatinine at three and six months. Actuarial one year patient (100 vs. 95%) and graft (97 vs. 91%) survival, KNW vs. controls respectively, are excellent to date. Further analyses showed no differences in outcome variables between recipients of KNW versus controls when the donor age was > or =60 years. Similar outcome was achieved by transplanting both kidneys from a KNW donor into a single recipient as compared with single-kidney transplantation from control donors. Careful donor-recipient pairing using kidneys from advanced-age donors for smaller, advanced-age recipients provided good short-term outcome. In conclusion, there was no significant difference in short-term outcome in recipients of KNW versus controls despite differences in donor age and lowest total 4-hr urine output. We believe that, with careful consideration, existing donor selection criteria can be expanded to include certain donors previously considered unusable.

Adult↗
PubMed1996

Coexistence of Th1- and Th2-type cytokine profiles in anti-CD2 monoclonal antibody-induced tolerance.

Anti-CD2 monoclonal antibody OX34 has been shown to suppress immunity in rodents in vitro and in vivo. To evaluate the effects of OX34 on vascularized allografts, Lewis (RT1(1)) hearts were transplanted heterotopically into Wistar Furth (RT1(u)) rats. A single 5 mg/kg intraperitoneal dose of OX34 administered at transplantation induced indefinite graft survival (mean survival time >140.3+/-12.3 vs. 12.7+/-0.7 control, P=0.001). The mixed lymphocyte response was partially inhibited at 60 days after transplant, returning to normal at 100 days. Donor-specific tolerance was confirmed by acceptance of second donor (>100 days, n=2) and rejection of third-party (mean survival time: 7.5+/-0.5 days, n=2) hearts. Immunohistochemical staining of allograft tissue from tolerant animals demonstrated abundant CD2+, CD4+, and CD8+ graft-infiltrating cells. To elucidate further the nature of these cells, we compared the expression of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma mRNA in allografted tissue from tolerant, acutely rejecting (AR), isografted, and naive animals using nonisotopic in situ hybridization. A significant increase in IL-2, IL-4, IL-10, and IFN-gamma mRNA was observed in graft-infiltrating cells of both tolerant and AR animals. IL-10 mRNA expression 4 days after transplant was significantly elevated in the OX34-treated compared to AR recipients. These data demonstrate that a single dose of OX34 at engraftment induces tolerance to vascularized allografts. Expression of both T helper 1 and T helper 2 cytokine mRNA profiles (IL-2/IFN-gamma and IL-4/ IL-10, respectively) are up-regulated locally in graft-infiltrating cells of AR and tolerant animal allografts.

Animals↗
PubMed1996

The use of bilateral adult renal allografts - a method to optimize function from donor kidneys with suboptimal nephron mass.

Alternatives to traditional organ donor usage has allowed expansion of the organ donor pool to help compensate for the increasing disparity between recipients and donors. The use of bilateral adult renal transplants is a novel idea to salvage older donor kidneys with suboptimal nephron mass that would otherwise be destined for discard. Ten renal transplants were performed utilizing both kidneys from adult cadaver donors with diminished nephron mass determined by calculated glomerular filtration rate or biopsy evidence of significant glomerulosclerosis (>10%). Nine of ten (90%) recipients have satisfactory renal function at a mean follow-up of 7 months. The single case of graft failure was due to documented medical non-compliance. Mean serum creatinine at 6 months was 1.5 mg/dl. Mean measured creatinine clearance was 43.2+/-3.4. These preliminary findings suggest that the use of bilateral renal transplants provide satisfactory early function and allows salvage of older donor kidneys with suboptimal nephron mass.

Adolescent↗
PubMed1996

CO2 angiography--a technique for vascular imaging in renal allograft dysfunction.

Use of iodinated contrast for vascular imaging can be associated with nephrotoxicity and hypersensitivity reactions. Renal injury following conventional angiography is more likely to manifest in the setting of preexisting renal dysfunction. In the setting of suboptimal renal allograft function, these considerations are particularly relevant. Recently, CO2 has received attention as a nontoxic, injectable, rapidly absorbed gas that is a cost-effective alternative to standard contrast agents in high-risk patients, such as renal transplant recipients. We report the clinical course of a patient with transplant renal artery stenosis and a serum creatinine of 2.8 mg/dl who has successfully undergone angiography and percutaneous transluminal angioplasty using CO2 as the sole contrast agent. This case illustrates the potential use for CO2 as a contrast agent for vascular imaging in patients with suboptimal renal function who require definitive vascular imaging or therapy.

Adult↗
PubMed1996

Cellular localization and effect of nitric oxide synthesis in a rat model of orthotopic liver transplantation.

Nitric oxide (NO) is a multifunctional free radical with a variety of described biochemical and physiological roles. The immunologic relationships between organ transplantation and NO synthesis are unknown. While a number of in vitro and in vivo models have demonstrated an immunomodulatory role for NO, results suggest both an immunosuppressive and immunostimulatory function. In order to better delineate the role of NO in liver transplantation, the Kamada model of rat OLT with strain combinations simulating acute rejection and spontaneous hyporesponsiveness was chosen. In this setting, both acute rejection and spontaneous hyporesponsiveness were associated with increased levels of plasma NO metabolites and allograft expression of the enzyme, NO synthase (iNOS). The extent of expression was significantly greater with acute rejection. Using in situ hybridization, iNOS mRNA was localized to both infiltrating inflammatory cells and hepatocytes in the context of acute rejection. In contrast, iNOS mRNA expression was isolated to the hepatocytes in the hyporesponsive state. To specifically delineate the role of hepatocyte-derived NO, NO synthesis was ablated in the spontaneous hyporesponsiveness model and resulted in significant elevation of serum transaminase values with accompanying histologic evidence of increased periportal inflammatory infiltration. Our results suggest that the site of NO production varies according to the immunologic status of the liver allograft, and hepatocyte-derived NO may be protective in the hyporesponsive state.

Animals↗
PubMed1996

Cardia allograft unresponsiveness using a posttransplant strategy : characterization of the graft infiltrate.

We evaluated a combined posttransplant strategy using antilymphocyte serum (ALS) at time of engraftment followed by low dose total lymphoid irradiation (TLI) and donor bone marrow cell (BMC) inoculation administered either intrathymically (IT) or intravenously (IV) in the vigorously rejecting strain combination DA into Lew recipients. Allograft survival was significantly prolonged with administration of ALS in combination with TLI and IT (105 +/- 28.6 days) or IV (106.8 +/- 28.6 days) BMC compared to administration of ALS combined with either TLI (17.8 +/- 0.4 days) or BMC (9.0 +/- 0.0 days), or TLI combined with BMC (1 1.5 +/- 0.5 days) (P < 0.000 1, experimental vs control animals). There was no difference in survival between those animals who underwent IT or IV BMC inoculation. Third-party (WF) BMC inoculation did not significantly prolong allograft survival (10.0 +/- 1.0 days). A mild to moderate cellular infiltrate was present in allograft tissue after 100 days. To further characterize these cells, cytokine mRNA expression in allograft tissue (> 100 days posttransplant) was evaluated using nonisotopic in situ hybridization. A similar cytokine profile was demonstrated in allograft tissue compared to naive and isograft tissue, except for a slight increase in IL-2 (P < 0.02, control vs IV BMC; P = NS, other groups). In summary, unresponsiveness was induced in a high-responder strain combination using a combined posttransplant strategy of ALS, TLI, and donor antigen either IT or IV. The cytokine profile of the graft infiltrating cells was similar to that of normal tissue. Unresponsiveness may be the result of functional inactivation of these cells.

Animals↗
PubMed1996

Double adult renal allografts: a technique for expansion of the cadaveric kidney donor pool.

BACKGROUND: A major impediment to kidney transplantation is the current shortage of donor organs. Currently approximately 22,500 candidates are awaiting kidney transplantation, while the number of donors remains stable at approximately 3500 each year in the United States. Alternative approaches to traditional organ donor selection are necessary. In this setting we hypothesized that kidneys with reduced nephron mass from adult donors may provide satisfactory renal function if both donor kidneys are placed into a single recipient. METHODS: Eighteen paired adult renal allografts were transplanted into nine adult recipients (DUAL). Recipient graft outcome variables were examined and compared with outcomes from single kidneys transplanted from randomly selected "ideal" donors younger than 50 years of age (CONT < 50) and "expanded" donors older than 60 years of age (CONT > 60) who underwent transplantation at our center. RESULTS: Six-month serum creatinine levels in the three groups, DUAL (n = 9), CONT < 50 (n = 20), and CONT > 60 (n = 12), were 1.6 +/- 0.3, 2.3 +/- 0.3, and 4.1 +/- 0.9 mg/dl, respectively, (p < 0.0001) between CONT > 60 and the other two groups. Mean estimated creatinine clearance (ml/min/1.73 m2) was 43.2 +/- 3.4, 62.5 +/- 5.4, and 24.5 +/- 5.3 (p < 0.02). Graft and patient survival at last follow-up in DUAL was 100% compared with 95% in CONT < 50 and 75% graft and 83% patient survival in CONT > 60. Delayed graft function occurred in one of nine patients (11%) in DUAL group compared with 4 of 20 (20%) in CONT < 50 group and 6 of 12 (50%) in CONT > 60 group. Mean follow-up of patients in DUAL group was 6.6 months (range, 2 to 14 months). CONCLUSIONS: Double adult kidney transplants (DUAL) are associated with acceptable short-term graft function, graft survival, and patient survival when compared with transplanted kidneys from an ideal donor group (CONT < 50). Double renal allografts are a preferred use for donor kidneys with suboptimal nephron mass. Long-term follow-up is required to validate further the proposed approach.

Adult↗
PubMed1996

Differential localization of allograft nitric oxide synthesis: comparison of liver and heart transplantation in the rat model.

Nitric oxide (NO) is a free radical with a diversity of cellular origins and potential functions. Within the realm of solid organ transplantation, NO has been the focus of much attention. Discordant reports have documented both suppression and potentiation of the alloimmune response. In addition to questions regarding its functional role, little is known of the cellular origins of NO in acute rejection of vascularized allografts. To address this question, acute rejection models of rat heterotopic heart and orthotopic liver transplantation were chosen. When compared with naive controls and isografted animals, acute rejection in both heart and liver transplantation was associated with elevated systemic levels of the NO metabolite, nitrite. This was accompanied by increased graft content of iNOS protein as determined by immunoblot analysis of protein extracts. Expression of iNOS mRNA was localized with in situ hybridization. In both heart and liver transplantation, iNOS mRNA was found in the inflammatory infiltrate accompanying acute rejection. In addition, hepatocytes also expressed iNOS mRNA in the rejecting liver allograft. In contrast, cardiac myocytes in the rejecting heart allograft did not stain for iNOS mRNA. These results indicate that organ-specific, differential cellular expression of iNOS occurs in the acutely rejecting allograft. Transcriptional regulation of iNOS may vary among various organs according to the local cellular milieu. In addition, there may be a variable allograft specific response to acute rejection which may modify the associated immunologic biology.

Acute Disease↗
PubMed1996

Necrotizing fasciitis.

Necrotizing fasciitis is an uncommon soft-tissue infection, usually caused by toxin-producing, virulent bacteria, which is characterized by widespread fascial necrosis with relative sparing of skin and underlying muscle. It is accompanied by local pain, fever, and systemic toxicity and is often fatal unless promptly recognized and aggressively treated. The disease occurs more frequently in diabetics, alcoholics, immunosuppressed patients, i.v. drug users, and patients with peripheral vascular disease, although it also occurs in young, previously healthy individuals. Although it can occur in any region of the body, the abdominal wall, perineum, and extremities are the most common sites of infection. Introduction of the pathogen into the subcutaneous space occurs via disruption of the overlying skin or by hematogenous spread from a distant site of infection. Polymicrobial necrotizing fasciitis is usually caused by enteric pathogens, whereas monomicrobial necrotizing fasciitis is usually due to skin flora. Tissue damage and systemic toxicity are believed to result from the release of endogenous cytokines and bacterial toxins. Due to the paucity of skin findings early in the disease, diagnosis is often extremely difficult and relies on a high index of suspicion. Definitive diagnosis is made at surgery by demonstration of a lack of resistance of normally adherent fascia to blunt dissection. Treatment modalities include surgery, antibiotics, supportive care, and hyperbaric oxygen. Early and adequate surgical debridement and fasciotomy have been associated with improved survival. Initial antibiotic therapy should include broad aerobic and anaerobic coverage. If available, hyperbaric oxygen therapy should be considered, although to our knowledge, there are no prospective, randomized clinical trials to support this. Mortality rates are as high as 76%. Delays in diagnosis and/or treatment correlate with poor outcome, with the cause of death being overwhelming sepsis syndrome and/or multiple organ system failure.

Fasciitis, Necrotizing↗