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D L Dunn

Publications and source records attributed to D L Dunn.

At least 73 records · Page 4Linked to original sources
PubMed1996

Vascular graft thrombosis after pancreatic transplantation: univariate and multivariate operative and nonoperative risk factor analysis.

BACKGROUND: Vascular thrombosis is still the leading cause of nonimmunologic, technical pancreatic transplant graft failures. The paucity of published data--coupled with our large institutional experience with pancreatic transplantation in all recipient and transplant categories, using a wide spectrum of surgical techniques--provided the impetus for a retrospective study of graft thrombosis risk factors. STUDY DESIGN: Four hundred thirty-eight patients with pancreatic transplants (45 percent simultaneous pancreas-kidney [SPK], 23 percent pancreas-after-kidney [PAK], and 32 percent pancreatic transplants alone [PTA] and with Type I insulin-dependent diabetes mellitus were studied retrospectively. Of 438 pancreatic transplants, 90 percent were bladder-drained and 10 percent were enteric-drained. Ninety-three percent were from cadaver donors, 90 percent were whole-organ grafts, and 20 percent were retransplantations. Quadruple immunosuppression was given. For bladder-drained, whole-organ transplantations (n=378), we performed Cox regression analyses to study the impact on pancreatic graft thrombosis of donor, recipient, mode of preservation, and surgical variables. RESULTS: The overall thrombosis rate was 12 percent (5 percent arterial, 7 percent venous). For cadaver, bladder-drained, whole-organ pancreatic transplants, the thrombosis incidence was highest in PAK recipients (20 percent). The PAK category was also found to be an independent risk factor for thrombosis by stepwise Cox regression analysis. In separate stepwise Cox regression analyses for each category, other identified risk factors for thrombosis included the following: donor age (PAK, PTA); cardiocerebrovascular cause of donor death (SPK, PAK); the use of an aortic Carrel patch (SPK); arterial pancreatic graft reconstruction using a splenic artery to superior mesenteric artery anastomosis (SPK, PTA) or an interposition graft between the splenic artery and the superior mesenteric artery (PTA); portal vein extension graft (PAK); left-sided implantation into the recipient (PAK); and graft pancreatitis (defined as hyperamylasemia exceeding five days post-transplant [PAK, PTA]). CONCLUSIONS: Older donors or those who died of cardiocerebrovascular disease should not be considered for any recipient category. Preservation time needs to be minimized and strategies need to be developed to decrease graft pancreatitis. Surgically, left-sided implantation and arterial reconstructions other than the Y-graft also increase risk, as do portal vein extensions. Renal transplants alone in prospective PAK recipients with Type I diabetes mellitus should, therefore, always be implanted left-sided to allow for right-sided pancreatic graft placement.

Adult↗
PubMed1996

Intra-abdominal fungal infections after pancreatic transplantation: incidence, treatment, and outcome.

BACKGROUND: Intra-abdominal infections account for 15 percent of technical failures after pancreatic transplantation. Although some data are available about intra-abdominal bacterial infections, no study has analyzed the incidence, treatment, and outcome of intra-abdominal fungal infections. STUDY DESIGN: We retrospectively studied 445 consecutive pancreatic transplantations--45 percent were simultaneous pancreatic and renal, 24 percent pancreatic after renal, and 31 percent pancreatic transplantations alone--in patients with Type I diabetes mellitus. Donors were cadavers in 92 percent and living relatives in 8 percent. Primary transplantations were done in 80 percent and retransplantation in 20 percent. Of these 445 pancreatic transplantations, 90 percent were bladder-drained, 9 percent enteric-drained, and 1 percent duct-injected. Only symptomatic patients with documented culture-positive intra-abdominal fungal infections were included. RESULTS: Intra-abdominal fungal infections occurred after pancreatic transplantation in 41 (9.2 percent) of 445 patients. Donor age, but not recipient age, was a significant risk factor. The rate of infections was higher for enteric-drained (21 percent) than for bladder-drained (10 percent) transplantations; for organs donated by living relatives (16 percent) than for those from cadavers (9 percent); and for pancreatic after renal (12 percent) and simultaneous pancreatic-renal (11 percent) than for pancreatic-only (5 percent) recipients. The rate of intra-abdominal fungal infections was 6 percent for recipients who were given antifungal prophylaxis (fluconazole, 400 mg/day for seven days after transplantation) compared with 10 percent for those without prophylaxis. The one-year graft survival rate for recipients with infection was 17 percent compared with 65 percent for those without (p = 0.0001); the survival rate was 70 percent compared with 92 percent for patients with and without infection, respectively (p = 0.0007). In 22 percent of recipients, the infection resolved and graft function persisted; in 58 percent, the infection resolved after transplant pancreatectomy; and in 20 percent, death occurred despite transplant pancreatectomy. Recipients with sole fungal or fungal and bacterial infection (n = 41) were 50 percent less likely to recover with a functioning graft and had a risk of death that was three times higher (p < or = 0.05) than those with sole bacterial infection (n = 48). CONCLUSIONS: Intra-abdominal fungal infections after pancreatic transplants are associated with high morbidity and mortality rates, significantly higher than for sole bacterial infections. In addition to aggressive treatment, including transplant pancreatectomy and reduction of immunosuppression, efforts must be made toward better prevention of intra-abdominal fungal infections.

Adult↗
PubMed1996

A third kidney transplant: cost-effective treatment for end-stage renal disease?

Given the organ donor shortage, some question whether a third kidney transplant can be justified. We studied the outcome of 51 third transplants (mean age 28 +/- 2 yr) done between 1 January 1985 and 31 December 1994. We compared hospital stay (mean +/- S.E.), cost, readmissions, readmission days, and outcome of third (vs. first and second) transplants. We found that patient survival for third transplants was equivalent to first and second transplants; graft survival was not as good. However, when third transplant recipients with recurrent disease (specifically, hemolytic uremic syndrome and focal sclerosis) were excluded from our analysis, we found no difference in 5-yr graft survival (vs. first or second transplant recipients). Of the 51 third transplant recipients, 41 had a cadaver donor transplant. Third cadaver transplant recipients tended to have a longer hospital stay (p = NS) than first cadaver transplant recipients but had no more readmissions or readmission days than first and second cadaver transplant recipients. Employment data are available for 28 third transplant recipients; 16 (57%) are currently working or going to school. Of the 21 recipients who responded to quality of life questionnaires, 17 (81%) reported being healthy and all 21 (100%) said transplantation was not a drawback to their health. We conclude that third transplants should be considered for selected patients with renal failure whose first and second transplants have failed. Such patients can often be successfully transplanted.

Actuarial Analysis↗
PubMed1995

A prospective study of FK506 versus CsA and pig ATG in a porcine model of small bowel transplantation.

Rejection remains a major barrier to successful bowel transplantation, and immunosuppressive protocols are far from standardized. In 88 nonrelated outbred pigs, we compared the effects of two immunosuppressive regimens--one with FK506, the other with cyclosporine (CsA) and pig antithymocyte globulin (ATG)--on incidence and severity of rejection in the early, critical posttransplant period. Group A (n = 14) was nonimmunosuppressed (controls). Group B (n = 17) received pig ATG (10 mg/kg/day x 10 days), CsA (3 mg/kg/day), prednisolone (2 mg/kg/day), and azathioprine (2.5 mg/kg/day); prednisolone and azathioprine were each reduced by 50% at 8 and 15 days posttransplant. Trough CsA whole-blood concentrations were > or = 400 ng/ml for the first 7 days, > or = 200 ng/ml thereafter. Group C (n = 13) received FK506 (0.2 mg/kg/day) and prednisolone (2 mg/kg/day); prednisolone was reduced by 50% at 8 and 15 days. FK506 whole-blood concentrations were > or = 20 ng/ml. All immunosuppression in groups B and C was given intravenously. We performed orthotopic small bowel transplants with systemic venous drainage. Recipient bowel was resected distal to the second portion of the duodenum and proximal to the rectum at transplant; bowel continuity was restored by duodenojejunostomy; ileostomy was created distally to allow access for daily biopsies. We graded interstitial and vascular rejection separately, according to a scoring system (no, mild, moderate, and severe rejection). Rejection-free graft survivals at 7, 14, and 21 days posttransplant were 38%, 19%, and 0% in group A; 93%, 93%, and 62% in group B; and 100%, 91%, and 82% in group C (P < 0.001). Comparing rejection in the immunosuppressed groups, group C (FK506) had a stronger tendency toward rejection than group B (CsA-ATG); significant differences between groups B and C were, however, noted only on individual days posttransplant, not over time. The death rate due to irreversible rejection was not significantly different in groups B and C (P = 0.8), but was significantly better in both of these immunosuppressed groups than in group A (P < 0.001). Pig survival was significantly longer in group C than in B (P = 0.001) due to a lower infection rate in group C. Posttransplant serum interleukin 2 and 7 levels did not correlate with rejection grades. Graft-versus-host reaction was noted only in the skin in 29% of group A, 73% of group B, and 77% of group C pigs; liver and native bowel were not involved.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Lymphocyte-derived cytokines augment macrophage tumor necrosis factor-alpha and interleukin-6 secretion during experimental gram-negative bacterial sepsis.

Although lymphocyte-derived cytokines are known to augment macrophage cytokine production in vitro, their effect on macrophage tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) secretion during gram-negative bacterial sepsis has not been characterized. The purpose of this study was to examine the effect of lymphocyte-derived cytokines on macrophage TNF-alpha and IL-6 secretion during gram-negative bacterial peritonitis. To examine this problem, uninfected and infected mice were studied. Mice were infected with Escherichia coli O111:B4 and two subgroups were examined consisting of those pretreated iv 1 hr prior to bacterial challenge with either (1) saline or (2) anti-E. coli O111:B4 LPS mAb 2A3, the latter administered to abrogate the effects of LPS in vivo. Thus, three groups of mice were studied in relation to pretreatment and infectious challenges: (1) saline/saline (control); (2) saline/E. coli (saline); and (3) mAb 2A3/E. coli (mAb 2A3). Nonadherent splenocytes (> 95% lymphocytes by histologic staining criteria) harvested 16 hr later from mice in each group were incubated in culture ex vivo for 3 hr to obtain supernatants containing lymphocyte-derived cytokines. These supernatants containing lymphocyte-derived cytokines then were incubated in vitro with naive splenic macrophages with or without E. coli O111:B4 LPS. Macrophage TNF-alpha and IL-6 levels were determined using L929 and B9 bioassays.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Antibody response of pediatric solid organ transplant recipients to immunization against influenza virus.

We studied the immunogenicity of the 1992-1993 trivalent split-virus influenza vaccine in pediatric solid organ transplant recipients (PSOTRs) and their healthy siblings. One month after immunization, 41 (82%) of 50 subjects achieved protective titers of antibodies to influenza A, and 30 (60%) to influenza B, rates similar to those in healthy siblings. Achievement and persistence of protective titers occurred significantly more often in children with preexisting antibody. We recommend annual immunization of PSOTRs, their household contacts, and health care workers; immunologically naive PSOTRs may benefit from immunization before transplantation.

Antibody Formation↗
PubMed1995

Peptide derivatives of three distinct lipopolysaccharide binding proteins inhibit lipopolysaccharide-induced tumor necrosis factor-alpha secretion in vitro.

BACKGROUND: Bactericidal permeability increasing protein (BPI), Limulus anti-lipopolysaccharide factor (LALF), and lipopolysaccharide binding protein (LBP) are three distinct proteins that bind to lipopolysaccharide (LPS). Intriguingly, binding of BPI and LALF to LPS results in neutralization of LPS activity, whereas the binding of LBP to LPS creates a complex that results in augmentation of LPS activity. Despite their different effector functions, we hypothesized that peptides based on the sequences of the proposed LPS-binding motif from each protein would neutralize LPS in vitro. METHODS: Three peptide sequences, each 27 amino acids in length, of the proposed LPS-binding motif of BPI (BG38), LALF (BG42), and LBP (BG43) were synthesized. These peptides were then tested for their: (1) ability to inhibit macrophage secretion of TNF-alpha after stimulation by LPS derived from Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens; and (2) bactericidal activity against these same four gram-negative bacteria in vitro. RESULTS: Synthetic peptides BG38 (BPI-derived), BG42 (LALF-derived), and BG43 (LBP-derived) but not control peptide significantly inhibited LPS-induced tumor necrosis factor-alpha secretion by macrophages and mediated the lysis of gram-negative bacteria in vitro. In addition, preincubation of LPS with peptide BG38 mediated complete protection subsequent to lethal endotoxin challenge. CONCLUSIONS: These data demonstrate that small peptides derived from BPI, LALF, and LBP retained significant endotoxin-neutralizing and bactericidal activity against many different gram-negative bacteria in vitro. Identification of this conserved LPS-binding region within each protein may aid in the development of new immunomodulatory reagents for use as adjuvant therapy in the treatment of gram-negative bacterial sepsis.

Acute-Phase Proteins↗
PubMed1995

Stool carriage, clinical isolation, and mortality during an outbreak of vancomycin-resistant enterococci in hospitalized medical and/or surgical patients.

During a nosocomial outbreak of infection due to vancomycin-resistant enterococci (VRE), rectal swabs that were collected weekly were used to identify and isolate VRE carriers. Over 6 months, 1,458 stool specimens from 724 high-risk patients were cultured, and 187 VRE isolates were recovered from 61 patients; 96% of the isolates were Enterococcus faecium. VRE tended to be isolated from clinical specimens from patients identified as VRE carriers by stool surveillance (P < .01). However, isolation of VRE from surveillance cultures preceded clinical isolation for only approximately 50% of the patients from whom a clinical VRE isolate was recovered. Mortality was greater (P < .05) among patients from whom a clinical VRE isolate was recovered than among patients from whom VRE was isolated only by stool surveillance. The mortality (1[17%] of 6) among patients for whom VRE was isolated from blood was similar to that (10 [27%] of 37) among patients for whom vancomycin-susceptible enterococcus was isolated from blood (P = .97). Despite prompt initiation of contact precautions for VRE carriers, the incidence of fecal carriage of VRE remained approximately 8% among this patient population for the 6-month period of the study.

Adult↗
PubMed1995

Short- and long-term outcomes of kidney transplants with multiple renal arteries.

OBJECTIVE: The authors determined whether the use of kidney allografts with multiple renal arteries adversely effects post-transplant graft and patient outcome or increases the incidence of vascular and urologic complications. BACKGROUND: Kidney grafts with multiple renal arteries have been associated with an increased incidence of early vascular and urologic complications. Kidney transplants with single versus multiple renal arteries have not been compared in regard to long-term graft and patient outcome or post-transplant incidence of hypertension, acute tubular necrosis, rejection, and late vascular and urologic complications. METHODS: We analyzed 998 adult kidney transplants done from December 1, 1985 through June 30, 1993, in which only the recipient's external or internal iliac artery was used for anastomosis. We divided the study population into 3 groups: Group A-1 renal artery, 1 arterial anastomosis (n = 835), Group B-->1 renal artery, 1 arterial anastomosis (n = 112), Group C-->1 renal artery, > 1 arterial anastomosis (n = 51). We compared the incidence of post-transplant hypertension, acute tubular necrosis, acute rejection, and vascular and urologic complications; mean creatinine levels at 1, 3, and 5 years post-transplant; and patient and graft survival. Univariate and multivariate analyses were done to identify risk factors for vascular complications. RESULTS: We found no significant differences among the three groups for the following variables: post-transplant hypertension, acute tubular necrosis, acute rejection, creatinine levels, early vascular and urologic complications, and graft and patient survival. In kidneys with single arteries, the presence (vs. absence) of an aortic patch and the type of the arterial anastomosis (end-to-end to the hypogastric vs. end-to-side to the external iliac artery) did not have an impact on the incidence of early or late vascular complications. In kidneys with multiple arteries, only the rate of late renal artery stenosis was higher, the rate of early vascular and urologic complications was not different. Our multivariate analysis identified acute tubular necrosis as a risk factor for renal artery and vein thrombosis; graft placement on the left side for arterial thrombosis; and preservation time > or = 24 hours and multiple renal arteries for renal artery stenosis. CONCLUSIONS: Results of kidney transplants using allografts with multiple versus single arteries are similar.

Adolescent↗
PubMed1995

Autologous islet transplantation to prevent diabetes after pancreatic resection.

BACKGROUND: Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent. OBJECTIVE: Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis. PATIENTS AND METHODS: Of the 48 patients, 43 underwent total or near-total (> 95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables. RESULTS: One perioperative death occurred. Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received > 300,000 islets, 74% were insulin independent at > 2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = -0.52, p = 0.006) and the dispersion method (p = 0.005). CONCLUSION: Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.

Adolescent↗
PubMed1995

Validating the Resource-Based Relative Value Scale cross-specialty alignment. A survey of double-boarded physicians.

In 1992, Medicare changed significantly how it paid physicians: instead of basing payment rates on charges, the federal government established a fee schedule based on the Resource-Based Relative Value Scale (RBRVS). Central to the development of the RBRVS was the methodology used to align the work of all specialties onto a single, common scale, termed "cross-specialty alignment." This article presents the methods and results of an alternative approach to cross-specialty alignment. We surveyed physicians who were board certified in both pathology and internal medicine (double-boarded) and asked them about the work of services in both specialties. The results provide a natural bridge between the work of the two specialties. The double-boarded survey results agreed closely with the RBRVS findings. Furthermore, the findings were robust after weighting the estimates by how frequently a physician performs a service or after grouping the physicians by the mix of services in their practice. We conclude that the relative work positions of pathology and internal medicine in the RBRVS have validity. Our findings suggest that a survey of physicians with expertise in multiple specialties is a useful approach for developing cross-specialty linkages for an RBRVS or for validating existing linkages.

Adult↗
PubMed1995

Evaluation of CMV-vue antigenemia assay for rapid detection of cytomegalovirus in mixed-leukocyte blood fractions.

The CMV-vue antigenemia assay was evaluated by using mixed-leukocyte (ML) blood fractions. Of 234 ML fractions studied, 32 (14%), 23 (10%), and 20 (8.5%) were positive in the CMV-vue assay and conventional and shell vial cultures, respectively. The CMV-vue assay was more sensitive than shell vial cultures for rapid detection of cytomegalovirus. ML fractions are appropriate specimens for the cytomegalovirus antigenemia assay.

Antigens, Viral↗
PubMed1995

Economies of scope in physicians' work: the performance of multiple surgery.

While the fees for the large majority of physicians' services in the new Medicare Fee Schedule (MFS) are derived directly from studies of the resource costs involved, payments for one class of procedures, multiple surgery, are based instead on existing policies and conventions. Using surveys of physicians, we measured the work and time involved in performing 146 multiple surgeries. We found economies of scope exist in performing these services, particularly during the preoperative and postoperative periods. We also found some differences in economies across procedures. Based on our findings, we propose payment policies for multiple surgery.

Fee Schedules↗
PubMed1995

Incidence, complications, treatment, and outcome of ulcers of the upper gastrointestinal tract after renal transplantation during the cyclosporine era.

BACKGROUND: Ulcers of the upper gastrointestinal tract after renal transplantation have been reported as a frequent and often lethal complication. Considering the continuous expansion of renal recipient criteria, we reviewed our experience with post-transplant ulcers after 1,034 renal transplants performed during the cyclosporine era. STUDY DESIGN: Our retrospective study analyzed only endoscopy-proven ulcers of the esophagus, stomach, and duodenum in 439 (42 percent) living related adult recipients and 595 (58 percent) cadaver or living unrelated adult recipients. For ulcer prophylaxis, only oral antacids were routinely given post-transplant. RESULTS: There were 41 ulcers in 33 patients (esophageal: n = 5, 12 percent; gastric: n = 17, 42 percent; duodenal: n = 19, 46 percent). Significant complications (n = 16) included 15 bleeding episodes and one perforation. The pathogenesis was viral in seven cases (gastric: n = 6, 15 percent; duodenal: n = 1, 2 percent). The ulcers occurred significantly earlier post-transplant in cadaver or living unrelated compared with living related recipients (median, 53 compared with 508 days, p = 0.02). Nonoperative treatment was successful for 96 percent of all ulcers. We found no ulcer-related mortality or graft loss. For living related recipients, the actuarial graft survival rate at three years was 69 percent for patients with ulcers compared with 86 percent for those without ulcers (p = 0.02); for cadaver or living unrelated recipients, it was 48 percent for patients with ulcers compared with 77 percent for those without ulcers (p = 0.9). For living related recipients, the actuarial patient survival rate at three years was 92 percent for patients with ulcers compared with 93 percent for those without ulcers (p = 0.8); for cadaver or living unrelated recipients, it was 59 percent for patients with ulcers compared with 88 percent for those without ulcers (p = 0.002). CONCLUSIONS: With more specific immunosuppression and more effective antiviral therapy, the incidence of post-transplant ulcers is low. Considering the excellent results of nonoperative ulcer therapy and a zero percent ulcer-related mortality rate, renal transplantation is safe for patients with specific (e.g., ulcer history) as well as nonspecific (e.g., chronic obstructive pulmonary disease) ulcer risk factors.

Adolescent↗