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D L Dunn

Publications and source records attributed to D L Dunn.

At least 145 records · Page 8Linked to original sources
PubMed1992

Protective anti-lipopolysaccharide monoclonal antibodies inhibit tumor necrosis factor production.

Elevated systemic levels of tumor necrosis factor (TNF) have been directly correlated with increased mortality during experimental gram-negative bacterial sepsis. Although monoclonal antibodies (mAbs) directed against gram-negative bacterial lipopolysaccharide (endotoxin, LPS) decrease TNF production in vitro and enhance survival in vivo, the precise relationship between inhibition of TNF secretion and protective capacity has not been defined. We hypothesized that protective anti-LPS mAbs inhibited LPS-stimulated TNF production. To test this hypothesis, we first produced and characterized three anti-LPS mAbs. We then examined the ability of these mAbs to decrease TNF secretion in an in vitro assay using cells from the murine macrophage cell line RAW 264.7. Subsequently, we assessed the protective capacities of these anti-LPS mAbs in a murine mucin peritonitis model of sepsis using live Escherichia coli 0111:B4 bacterial challenge. Our results demonstrated that those anti-LPS mAbs that decreased LPS-stimulated TNF secretion in vitro were protective in vivo. We concluded that inhibition of TNF secretion in vitro reflected protective capacity and that anti-LPS mAbs may confer protection via abrogation of macrophage TNF secretion. Inhibition of TNF production in vitro may provide a valuable test that may facilitate the selection of protective anti-LPS mAbs.

Animals↗
PubMed1992

Endotoxin promotes synergistic lethality during concurrent Escherichia coli and Candida albicans infection.

Previous studies have suggested that the lipopolysaccharide (LPS, endotoxin) component of the gram-negative bacterial cell wall is a key virulence factor that serves to enhance mortality during infections in which fungi and gram-negative bacteria are copathogens. To test this hypothesis, mice were challenged ip with Escherichia coli 0111:B4, Candida albicans, or both, and the effect of administration of anti-E. coli 0111:B4 LPS monoclonal antibody (mAb) 8G9 on endotoxemia, bacteremia, and mortality was assessed. E. coli (2 x 10(7) colony-forming units (CFU)) plus C. albicans (6 x 10(7) CFU) infection produced 100% mortality at 7 days, compared to the relatively low mortality caused by infection with either E. coli or C. albicans alone (20 and 3%, respectively, P less than 0.01). Administration of mAb 8G9 to animals receiving both pathogens reduced mortality (100% versus 14%, P less than 0.05), endotoxemia (3653 +/- 3187 versus 2 +/- 2 endotoxin units (EU), P less than 0.01), and bacteremia (4.2 +/- 2.3 versus 1.1 +/- 2.1 log(CFU/ml), P less than 0.01) compared to animals receiving saline alone. In a separate series of experiments, purified E. coli 0111:B4 LPS was administered in place of viable E. coli. The simultaneous injection of 200 micrograms E. coli LPS and C. albicans (6 x 10(7) CFU) produced 93% mortality at 7 days, compared to the low mortality that occurred following injection with either E. coli 0111:B4 LPS or C. albicans alone (21 and 3% respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

B-cell lymphoproliferative disorders in solid-organ transplant patients: detection of Epstein-Barr virus by in situ hybridization.

B-cell lymphoproliferative disorders (BLPDs) occur in approximately 2% of transplant recipients and are frequently fatal. Indirect serologic evidence has implicated Epstein-Barr virus (EBV) as an etiologic factor in these lesions. Direct evidence of the presence of EBV in these lesions has been obtained in relatively few cases. We used in situ hybridization (ISH) with a probe for the BamHI-W region of the EBV genome to study 52 tissue specimens from 28 solid-organ transplant patients who had BLPD. Epstein-Barr virus-infected lymphoid cells were identified in 26 of these 28 patients. The two patients without ISH evidence of EBV infection showed no distinctive clinical, morphologic, or serologic features. Previous filter-hybridization studies of these two patients had demonstrated evidence of EBV infection. Seven additional transplant patients without evidence of BLPD were studied as controls and showed no evidence of EBV in their lymphoid cells by ISH. These data provide further support for the etiologic role of EBV in the pathogenesis of posttransplantation lymphoproliferative disorders.

Adolescent↗
PubMed1992

Simultaneous pancreas-kidney transplant versus kidney transplant alone in diabetic patients.

The decision for simultaneous pancreas-kidney (SPK) versus kidney transplant alone (KTA) in diabetic patients with renal failure depends on the potential risks and benefits for each procedure. The purpose of this study was to compare the morbidity, mortality, and renal allograft survival in diabetic patients who underwent SPK versus KTA, and to discern the added risks associated with pancreas transplantation. Between 7/1/86 and 9/30/90, 69 primary cadaver SPK and 59 primary cadaver KTA were performed in type I diabetic patients with chronic renal failure. Antilymphocyte globulin or OKT3 was used for induction therapy, followed by standard triple therapy (prednisone, azathioprine, and cyclosporine). Patient and graft survivals were retrospectively analyzed. In addition, a detailed comparison of morbidity in those patients treated after 7/1/87 was performed (53 SPK, 49 KTA). For those less than 45 years of age (65 SPK, 42 KTA), there were no significant differences (P greater than 0.6) in the actuarial patient survival at one year (SPK 92%, KTA 95%), or two years (SPK 89%, KTA 92%), or actuarial renal allograft survival at one year (SPK 82%, KTA 83%) or two years (SPK 77%, KTA 83%). However, for those greater than 45 years old, actuarial renal allograft survival was significantly higher (P less than 0.03) in the KTA group. The mean serum creatinine levels were similar at one year (SPK 1.8, KTA 1.9 mg/d).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Donor hyperglycemia as a minor risk factor and immunologic variables as major risk factors for pancreas allograft loss in a multivariate analysis of a single institution's experience.

The impact of multiple donor and recipient variables on functional survival of 307 cadaveric pancreas allografts transplanted in 253 recipients at the authors' institution between July 25, 1978 and September 4, 1990 was determined using the Cox proportional hazards regression model. Relative risk of graft loss was calculated for all cases as well as for technically successful (TS) ones. Factors with an impact in descending order of significance for TS cases were immunosuppression (RR = 3.9 for double-drug versus triple-drug maintenance, p less than 0.0001); recipient category (RR = 2.4 for pancreas alone versus simultaneous pancreas/kidney, p = 0.009); retransplantation (RR = 1.8 for retransplants versus primary grafts, p = 0.007); donor hyperglycemia (RR = 1.7 for blood glucose greater than or equal to 200 versus less than 200 mg/dL, p = 0.02); human leukocyte antigen (HLA) matching (RR = 2.1 for poor versus a good match, p = 0.04). A logistic regression analysis also was performed to determine which factors predisposed to technical failure; none were identified. To make the model as relevant as possible to their current program, the authors analyzed only the bladder-drained cases (n = 221; 1984 to 1990). All patients received triple therapy. Recipient category, retransplantation, donor hyperglycemia, and degree of HLA matching remained as significant risk factors. Construction of estimated survival curves showed that the results of retransplantation were significantly improved, and the penalty incurred by using hyperglycemic donors was partially ameliorated by using well-matched donors. Because preservation times up to 30 hours did not exert an adverse effect on outcome, an argument is made to share pancreata between centers to achieve good matches.

Female↗
PubMed1992

Conversion of exocrine secretions from bladder to enteric drainage in recipients of whole pancreaticoduodenal transplants.

Between September 1984 and August 1991, 265 whole pancreaticoduodenal transplants were done at our institution, with bladder drainage of exocrine secretions through a duodenocystostomy. Seventeen patients subsequently underwent conversion from bladder to enteric drainage at 2 to 64 months after transplant. Eight conversion procedures were done to correct chronic intractable metabolic acidosis due to bicarbonate loss from the allograft: seven to alleviate severe dysuria, presumed secondary to the action of graft enzymes on uroepithelium; one to prevent recurrent allograft pancreatitis, presumed secondary to back pressure from the bladder; and one because of graft duodenectomy for severe cytomegalovirus duodenitis with perforation. None were done to correct technical complications from the initial transplant operation. The conversions were done by dividing the graft duodenocystostomy, then re-establishing drainage through a graft duodenal-recipient jejunal anastomosis. A simple loop of recipient jejunum was used for the duodenojejunostomy in 15 cases, and a Roux limb in two. One of those two cases had a previously created Roux limb that was available for use. The other was in the patient who underwent graft duodenectomy and subsequent mucosa-to-mucosa anastomosis of the pancreatic duct to a newly created Roux limb of jejunum. All patients experienced relief of their symptoms after operation. Two patients had surgical complications (12%), an enterotomy in one case, which was closed operatively, and an enterocutaneous fistula in the other case, which healed spontaneously with bowel rest and parenteral nutrition. The drawback to conversion is loss of urine amylase as a marker for rejection, particularly in recipients of solitary pancreas grafts (n = 5). In recipients of simultaneous pancreas-kidney (SPK) allografts (n = 12), the kidney can still be used to monitor for rejection (two with follow-up < 1 year, 10 with follow-up > 1 year). None of our solitary pancreas recipients, however, have lost graft function (follow-up, 10 to 36 months). The only pancreas allograft loss was in an SPK recipient who also rejected the kidney 6 months after conversion. She received a second SPK transplant with enteric drainage, and is insulin independent and normoglycemic 10 months after retransplantation. Patients converted for metabolic acidosis tended to have impaired renal function (mean creatinine, 2.14 +/- 0.98 mg/dL at time of conversion) due to chronic rejection, progression of native kidney diabetic nephropathy, or cyclosporine toxicity, and possibly could not compensate for bicarbonate loss from the pancreas allograft.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

An overview of the development and refinement of the Resource-Based Relative Value Scale. The foundation for reform of U.S. physician payment.

Responding to distortions in payment rates between services, policymakers in the United States have sought a systematic and rational foundation for determining physician fees. One such approach to paying physicians, the Resource-Based Relative Value Scale (RBRVS), determines fees by measuring the relative resource costs required to produce them. On January 1, 1992, the Medicare program implemented a new payment system for physician services based on the RBRVS. This article provides a brief history of the RBRVS and a summary of the methods and data used to derive it. This overview represents the culmination of 6 years of research by the Harvard RBRVS study team and provides a road map to the study's concepts and definitions. The overview also provides a context for the articles in this issue that describe five major studies undertaken since 1988. The study's overall results are presented in the last article of the series.

Data Collection↗
PubMed1992

Predicting the work of evaluation and management services.

Physicians, carefully adhering to the definitions of Physicians' Current Procedural Terminology (CPT) billing codes, used the same CPT codes to denote evaluation and management services that varied widely in work and used different codes for services whose work was the same. As payment shifted to the Medicare Fee Schedule, it was important that the coding system be redefined so that codes consistently reflect the resource costs of these services. Redefining these codes for a resource-based payment system required an understanding of how verifiable predictors relate to physician work. Using data obtained from the Resource-Based Relative Value Scale (RBRVS) study regarding 377 services surveyed among physicians in 31 specialties, multiple regression analyses of the relationship of different variables to the mean values of work were performed. Intraservice time, which accounted for 90% of the variance, was the most important predictor of intraservice work. Specification of time, which previously had not been an element in the definitions of CPT codes for evaluation and management services, was useful in refining these codes so that their value corresponds more closely to resource costs. Other predictors of work were site of service or visit type, patient status (new/initial, established/subsequent), and referral status (consultation, nonconsultation).

Abstracting and Indexing↗
PubMed1992

Results and impacts of the Resource-Based Relative Value Scale.

On January 1, 1992, the Health Care Financing Administration implemented the 1989 legislation reforming the Medicare payment system for physicians' services. The cornerstone of the new payment reform is the Medicare Fee Schedule (MFS), which is based on the Resource-Based Relative Value Scale (RBRVS). In this article, the major findings of the RBRVS study and its impacts on physician payment are summarized. The authors report the impacts of a RBRVS-based fee schedule on Medicare fees and physicians' income if it were fully implemented, assuming budget neutrality and absence of volume changes in services. Under this scenario, fees for evaluation and management services increase by 15% to 45%, while fees for invasive services and diagnostic tests decrease by 20% to 30%. These changes increase the Medicare income of family practitioners by more than 30% while decreasing the income of most surgical specialties by 10% to 20%.

Economics, Medical↗
PubMed1992

Renal transplant function after ten years of cyclosporine.

Although the nephrotoxic side effects of cyclosporine are well known, the impact of long-term CsA on renal transplant function is uncertain. We studied 5-10-year renal function in 347 CsA-treated patients, and in 64 randomly selected non-CsA-treated patients who had a minimum of 55 months of graft function. Non-CsA patients had a lower creatinine (Cr) level at one year than CsA patients (P = .001), with no change in renal function over time (P = .6). In CsA-treated patients there was also no suggestion of progressive renal damage, as evidenced by no change in Cr or 1/Cr. Simple linear regression models of 1/Cr vs. time for the first 10 years posttransplant were fit to the data for each patient. Analysis of the Y-intercept estimates from these regressions showed that age (P = .001), sex (P = .001), cyclosporine toxicity (P = .024), and initial cyclosporine dosage (P = .016) significantly affected the one-year serum Cr. Variables not affecting one-year Cr included donor source, early rejection episodes, late rejection episodes, ATN, diabetes, transplant number, HLA ABDR mismatch (for cadaver transplants), maximum PRA, and PRA at transplant. Analysis of the slope estimates from the regressions revealed that only age (P = .001) and late rejection episodes (P = .001) significantly affected the rate of change in 1/Cr over time. We conclude that, in long-term renal transplant patients, there is no evidence of progressive deterioration in renal function due to CsA nephrotoxicity.

Creatinine↗
PubMed1992

Sequential therapy--a prospective randomized trial of MALG versus OKT3 for prophylactic immunosuppression in cadaver renal allograft recipients.

We prospectively studied the use of prophylactic Minnesota antilymphocyte globulin vs. OKT3 in kidney transplant recipients. Between 7/1/87 and 9/1/90, 138 adult kidney and 35 kidney-pancreas recipients were randomized after stratification for age (18-49 vs. greater than or equal to 50), diabetes (diabetic vs. nondiabetic), transplant number (1 vs. greater than 1) and, for retransplants, the length of survival of the first graft (less than 1 year vs. greater than or equal to 1 year), and then randomized to receive 7 days of either MALG (20 mg/kg/day) or OKT3 (5 mg/day). Immunosuppression was otherwise identical in both groups; prednisone and azathioprine started on the day of surgery, and cyclosporine started on postoperative day 6. Minimum follow-up was 9 months. There was no difference in one- and two-year actuarial patient or graft survival rates, incidence of rejection, or serum creatinine level. MALG was associated with a higher incidence of cytomegalovirus; it was statistically significant in the subgroup of CMV seronegative recipients of kidneys from seropositive donors (P less than .05). OKT3 was more expensive and was associated with significantly more side effects: fever (P less than .0001), dyspnea (P = .04), and acute respiratory distress syndrome (ARDS) (P = .02).

Adolescent↗
PubMed1992

Cytomegalovirus (CMV) antigenemia assay is more sensitive than shell vial cultures for rapid detection of CMV in polymorphonuclear blood leukocytes.

We compared the cytomegalovirus (CMV) antigenemia assay with shell vial cultures of polymorphonuclear leukocyte (PMNL)-enriched blood fractions for rapid diagnosis of CMV viremia. PMNL fractions of 280 blood specimens from 171 patients (170 solid-organ transplant recipients and 1 patient undergoing pretransplant evaluation) were inoculated in shell vial and conventional CMV cultures. A commercially available kit (CMV-vue kit; INCSTAR Corp.) was used for the CMV antigenemia assay, in which PMNL preparations were stained with monoclonal antibodies directed against the CMV protein pp65. Mixed-leukocyte blood fractions from the same blood specimens were inoculated in parallel shell vial and conventional cultures. CMV viremia (defined by the isolation of CMV in conventional cultures) was detected in 32 (13%) of 245 PMNL fractions included in the final analysis. Twenty-eight (87.5%) were also positive in the CMV antigenemia assay, whereas 22 (69%) were positive in shell vial cultures. Ten (4%) additional PMNL fractions positive only in the CMV antigenemia assay were from eight patients with active CMV infections (six patients), who had previous or subsequent episodes of CMV viremia (seven patients), or in whom CMV was isolated in cultures of simultaneously obtained mixed-leukocyte fractions (three patients). Overall, the CMV antigenemia assay was significantly more sensitive than shell vial cultures for detection of CMV in the PMNL fraction of blood leukocytes (P < 0.01, McNemar's test), and we recommend it as the method of choice for rapid diagnosis of CMV viremia.

Antigens, Viral↗
PubMed1992

Continual intracavitary administration of amphotericin B as an adjunct in the treatment of aspergillus brain abscess: case report and review of the literature.

Aspergillus brain abscess is often a fatal disease, regardless of the mode of therapy. Most often seen in the compromised host, it is notoriously refractory to systemic antifungal agents and intrathecal antimycotics. Even with radical surgical debridement, only 13 patients, including the present case, have survived longer than 3 months after being treated for aspergillus brain abscess or granuloma. Studies have shown poor penetration of amphotericin B into the brain and cerebrospinal fluid. One way to achieve therapeutic levels of the agent near the abscess is through the direct introduction of the agent into the abscess site via an indwelling catheter. In the present case, a woman with an aspergillus abscess of the left temporal lobe was treated by a combination of systemic agents, radical debridement, and local therapy, resulting in a cure with a follow-up of 6 years. This is the first reported instance of the use of long-term, local antifungal therapy delivered to the area of the abscess cavity, using a closed reservoir system, and this patient is only the second renal transplant patient reported to have survived aspergillus brain abscess. This form of treatment produced no untoward long-term side effects or neurological sequelae. Local irrigation with antifungal agents should be considered in conjunction with systemic antifungal drugs and drainage and/or debridement in cases of fungal intracerebral aspergilloma. This technique may also prove useful with other fungal brain lesions.

Adult↗
PubMed1992

Use of ganciclovir for cytomegalovirus infection.

Ganciclovir (9-(1,3-dihydroxy-2-propoxymethyl) guanine, DHPG) is an acyclovir analog with excellent antiviral activity against human cytomegalovirus (CMV). Clinically, CMV infection occurs in from 60 to 90% of all renal transplant recipients and it is responsible for significant patient morbidity and graft loss. The likelihood of infection is closely related to the CMV status of both donor and recipient, with the greatest risk arising in the combination of a seronegative patient receiving a seropositive organ. Intracellularly, DHPG is converted to DHPG-triphosphate, which competitively inhibits DNA polymerase. This conversion is accelerated up to 10-fold in virally infected cells, providing some selectivity of action. Uncontrolled studies demonstrated DHPG efficacy in CMV disease, but experience in children remains limited. Although bone marrow suppression is a major immediate toxicity, long-term concerns about carcinogenesis and infertility mandate careful patient selection. Recently at the University of Minnesota, 93 solid organ recipients (45 renal transplants) including some children have been treated for tissue-invasive CMV with DHPG. All had a characteristic clinical picture and either a positive CMV culture or a biopsy with CMV inclusions. The patients received i.v. DHPG (10 mg/kg/day) with appropriate adjustments for renal function. In renal allograft recipients, 89% recovered within 30 days, although 21% had to be retreated with DHPG. Although no patient died, allograft survival was significantly reduced (P = 0.02). An additional subgroup of patients (N = 18) who had both biopsy-proven rejection and invasive CMV disease were simultaneously treated for both processes. All of these patients recovered from their CMV infection, but two grafts were lost to rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1992

Kidney transplantation in patients with type I diabetes: 26-year experience at the University of Minnesota.

With current immunosuppressive protocols, 1- and 6-year graft survival is similar in diabetic and nondiabetic kidney transplant recipients. Living-donor transplant recipients have significantly better outcome. Death with function and chronic rejection remain the 2 predominant causes of graft loss for diabetic recipients. Compared with national statistics on diabetic patient survival on dialysis, our data suggest that transplantation is the treatment of choice for diabetic patients with end-stage renal disease.

Adolescent↗