Reimbursement for evaluation and management services.
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Humans↗
Biomedical subjects
D L Dunn
Publications and source records attributed to D L Dunn.
Cytomegalovirus disease recurrence after ganciclovir treatment in kidney and kidney-pancreas transplant recipients.
BACKGROUND: With the introduction of ganciclovir, the clinical pattern of cytomegalovirus (CMV) disease has changed; CMV disease recurrence after successful treatment of the initial episode has emerged as a more common problem. We studied CMV disease recurrence in kidney transplant (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients, and identified risk factors for recurrence. METHODS: Between January 1987 and December 1995, of 1272 KTx and 287 SPK recipients, 332 developed CMV disease and were treated with a 14-day course of i.v. ganciclovir, followed by a 10-week course of oral acyclovir. Among these 332 recipients, 103 (31%) developed CMV disease recurrence more than 30 days after treatment for the initial episode; this group was compared with those recipients who did not develop recurrence (n=229). Risk factors examined were age, presence of diabetes, type of transplant (KTx vs. SPK), donor source (cadaver vs. living donor), treatment for acute rejection, pretransplant CMV serologic status, evidence of tissue-invasive CMV, and treatment of the initial episode with human immune globulin in addition to ganciclovir. RESULTS: Univariate analysis found that patients with recurrence were more likely to be diabetic (70.9% vs. 53.7%; P=0.04), to have undergone an SPK (39.8% vs. 20.5%; P=0.004), to have received a cadaver organ (78.6% vs. 61.6%; P=0.002), and to have received treatment for acute rejection (78.6% vs. 59.8%; P=0.001). Using multivariate analysis, two statistically significant risk factors were found: receiving a cadaver organ (relative risk [RR]=1.90; P=0.03) and treatment for acute rejection (RR=2.02; P=0.008). Diabetes (RR=1.44; P=0.18) and a cadaver SPK transplant (RR=1.55; P=0.12) tended toward increased risk for recurrence, but the difference did not reach statistical significance. The remaining variables were not significant. Interestingly, CMV recurrence did not significantly diminish 5-year graft survival (52.0% vs. 54.4%; P not significant) or patient survival (67.0% vs. 68.3%; P not significant) rates. CONCLUSIONS: CMV disease recurs in roughly one-third of KTx and SPK recipients after treatment of the initial episode with ganciclovir. A cadaver organ source and treatment for acute rejection were the most significant clinical risk factors for recurrence. Clinical predictors of recurrence such as these may help to identify those recipients who need more intensive therapeutic and prophylactic regimens.
Antiviral Agents↗
Six years of surgical wound infection surveillance at a tertiary care center: review of the microbiologic and epidemiological aspects of 20,007 wounds.
HYPOTHESES: (1) Antibiotic restriction policies result in alteration of microbiologic features of surgical site infections (SSIs) and (2) reported SSI rates are underestimated when postdischarge surveillance is not included in SSI surveillance efforts. DESIGN: Retrospective analysis of prospectively collected SSI surveillance data. PATIENTS AND METHODS: We compared initial microbial isolates from SSIs between (1) January 1, 1993, and December 31, 1995, and (2) January; 1, 1996, and December 31, 1998. Antibiotic restriction policies were implemented at Fairview-University Medical Center, Minneapolis, Minn, on March 1, 1995. For the combined periods (January 1, 1993, to December 31, 1998), we determined SSI rates for 20007 operations according to the extent of bacterial contamination at surgery (wound class). Then, we analyzed SSI rates for 10559 of these operations (selected based on availability of Anesthesia Society of America score and type of procedure) using the surgical wound risk index (wound class, Anesthesia Society of America score, and length of operation). We categorized SSI rates by 17 procedures for comparison with SSI rates reported by 286 hospitals that contributed data confidentially and voluntarily to the National Nosocomial Infections Surveillance System in 1998. We compared SSI rates with and without postdischarge surveillance. RESULTS: Coagulase-negative staphylococcus and group D enterococcus were the 2 most frequent isolates before and after antibiotic restriction policies were implemented. Candida albicans isolates decreased from 7.9% (1993-1995) to 6.5% (1996-1998; P=.46). Methicillin-resistant Staphylococcus aureus (1.8% of isolates) and vancomycin-resistant enterococcus (2.4% of isolates) organisms were first identified between 1996 and 1998. Our SSI rates were 2.6% for class I wounds, 3.6% for class II wounds, and 10.5% for class III/IV wounds; 53.9% of SSIs were identified after hospital discharge. CONCLUSIONS: Antibiotic restriction policies did not alter the microbial spectrum of SSIs during the observation period. Reporting SSI rates in the absence of postdischarge surveillance dramatically underestimates actual SSI rates, especially in tertiary care hospitals that provide care for large populations of elderly and immunosuppressed patients.
Adolescent↗
Antiendotoxin agents share molecular homology within their lipopolysaccharide binding domains.
BACKGROUND: The purpose of this study was to determine whether antiendotoxin agents exhibit molecular homology within their lipopolysaccharide (LPS) binding domains, suggesting a common mechanism of action. We hypothesized that the presence of positively charged basic amino acids or a paucity of negatively charged acidic amino acids, or both, would be a critical characteristic of that portion of the molecule that binds to the highly negatively charged deep core/lipid A (DCLA) region of LPS. MATERIALS AND METHODS: We analyzed the amino acid sequences of the variable light (VL) and heavy (VH) chain complementarity-determining regions (CDRs) of anti-DCLA monoclonal antibodies (mAbs) 1B6, 5A5, and 7C5 and compared them with (1) the CDRs of three irrelevant control mAbs and (2) the LPS binding region of bactericidal permeability-increasing protein (BPI). We purified and amplified the specific nucleotide sequences of the variable regions using reverse transcriptase polymerase chain reaction. DNA was sequenced by dideoxy termination, and protein sequences were deduced and analyzed. The percentages of acidic, basic, polar, and hydrophobic amino acids within VH and VL chain CDRs were determined. RESULTS: We identified a paucity of negatively charged acidic amino acids exclusively within VL chain CDRs of anti-DCLA mAbs (P < 0.005). Although increased, the number of positively charged basic residues was not statistically significantly different; neither was the number of polar or hydrophobic amino acids. Conclusions. Our data suggest that the near absence of negatively charged acidic residues is critical for LPS binding. This characteristic appears to reside exclusively in the VL chain CDRs of anti-DCLA mAbs.
Amino Acid Sequence↗
Clostridium difficile colitis after kidney and kidney-pancreas transplantation.
OBJECTIVE: To determine the timing and risk factors involved in the development of Clostridium difficile (CD) colitis in kidney and kidney-pancreas transplant recipients. BACKGROUND DATA: The incidence of CD colitis after kidney and kidney-pancreas transplantation has not been studied in detail. The question of whether the immunosuppressed transplant recipient is more prone to CD colitis and its complications (i.e., megacolon, perforations) and the risk factors involved have not been determined. METHODS: We retrospectively reviewed our experience in kidney and kidney-pancreas recipients who received transplants between January 1, 1985 and December 31, 1994. We divided these recipients into three groups: pediatric kidney recipients, adult kidney recipients, and kidney-pancreas recipients. For each group, we assessed the timing of infection, primary disease, colitis treatment, and any concurrent complications or risk factors. RESULTS: Of 1932 transplants, 159 recipients developed post-transplant CD colitis. 132 charts were available for review. Forty-three pediatric kidney recipients developed CD colitis. Their mean age was 3.2 yr; 74% (n = 37) of them developed their colitis during their initial hospital stay, with the mean timing of infection being 33 d. Forty-one (95%) had undergone intra-abdominal placement of the graft, with renal artery anastomoses to the aorta. Fifty adult kidney recipients developed CD colitis. Thirteen (26%) developed colitis during their initial hospital stay, with the mean timing of infection (for all adult kidney recipients) being 15 months. Thirty-nine kidney-pancreas recipients developed CD colitis. Mean timing of infection was 6 months. The overall incidence of CD colitis was 8%, with 16% in the pediatric kidney group, 15.5% in the kidney-pancreas group, and 3.5% in the adult kidney group. The difference in mean timing of infection was significant between the three groups (p < 0.001 for pediatric versus adult kidney recipients, p = 0.002 for pediatric kidney versus kidney-pancreas recipients, and p = 0.2846 for adult kidney versus kidney-pancreas recipients). CONCLUSION: The incidence of CD colitis is increased in pediatric kidney and kidney-pancreas recipients. Young recipient age ( < 5 yr), female gender, treatment of rejection with monoclonal antibodies, antibiotic use, and intra-abdominal graft placement have been shown to increase the incidence of this disease. Further studies concerning prevention in the high-risk groups are needed.
Adolescent↗
Treatment of hospitalized patients with complicated gram-positive skin and skin structure infections: two randomized, multicentre studies of quinupristin/dalfopristin versus cefazolin, oxacillin or vancomycin. Synercid Skin and Skin Structure Infection Group.
Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic available for the treatment of complicated gram-positive skin and skin structure infections, was compared with standard comparators (cefazolin, oxacillin or vancomycin) in one USA and one international trial. These two randomized, open-label trials of virtually identical design enrolled a total of 893 patients (450 quinupristin/dalfopristin, 443 comparator). The majority of patients had erysipelas, traumatic wound infection or clean surgical wound infection. Staphylococcus aureus was the most frequently isolated pathogen in both treatment groups and polymicrobial infection was more common in the quinupristin/dalfopristin group than in the comparator group. The clinical success rate (cure plus improvement) in the clinically evaluable population was equivalent between the two treatment groups (68.2% quinupristin/dalfopristin, 70.7% comparator; 95% CI, -10.1, 5.1) despite a shorter mean duration of treatment for quinupristin/dalfopristin patients. In the bacteriologically evaluable population, by-patient and by-pathogen bacteriological eradication rates were somewhat lower for quinupristin/dalfopristin (65.8% and 66.6%, respectively) than for the comparator regimens (72.7% and 77.7%, respectively). The lower bacteriological response rates in the quinupristin/dalfopristin group were, in part, due to a higher rate of polymicrobial infections and a higher incidence of patients classified as clinical failure, a category which included premature discontinuation of treatment because of local venous adverse events. The bacteriological eradication rate for quinupristin/dalfopristin was higher in monomicrobial infections than in polymicrobial infections (72.6% versus 63.3%, respectively), whereas the corresponding rate for the comparator regimens was lower for monomicrobial infections than polymicrobial infections (70.8% versus 83.1%). This finding was not unexpected, since the spectrum of quinupristin/dalfopristin is focused on gram-positive pathogens and additional antibiotics to treat gram-negative bacteria were not required per protocol. The systemic tolerability of both treatment regimens was qualitatively similar. A higher rate of drug-related venous adverse events was reported for quinupristin/dalfopristin (66.2%) than for the comparator regimen (28.4%). Premature discontinuation of study drug was primarily due to adverse clinical events for quinupristin/dalfopristin (19.1%), whereas the most common reason for discontinuation among those receiving the comparator regimens was treatment failure (11.5%). Quinupristin/dalfopristin is an effective alternative for the treatment of hospitalized patients with complicated skin and skin structure infections due to quinupristin/ dalfopristin-susceptible gram-positive organisms, including methicillin- and erythromycin-resistant S. aureus.
Adolescent↗
Decreased acute rejection in kidney transplant recipients is associated with decreased chronic rejection.
OBJECTIVE: To determine whether a recent decrease in the rate of acute rejection after kidney transplantation was associated with a decrease in the rate of chronic rejection. SUMMARY BACKGROUND DATA: Single-institution and multicenter retrospective analyses have identified acute rejection episodes as the major risk factor for chronic rejection after kidney transplantation. However, to date, no study has shown that a decrease in the rate of acute rejection leads to a decrease in the rate of chronic rejection. METHODS: The authors studied patient populations who underwent transplants at a single center during two eras (1984-1987 and 1991-1994) to determine the rate of biopsy-proven acute rejection, the rate of biopsy-proven chronic rejection, and the graft half-life. RESULTS: Recipients who underwent transplantation in era 2 had a decreased rate of biopsy-proven acute rejection compared with era 1 (p < 0.05). This decrease was associated with a decreased rate of biopsy-proven chronic rejection for both cadaver (p = 0.0001) and living donor (p = 0.08) recipients. A trend was observed toward increased graft half-life in era 2 (p = NS). CONCLUSIONS: Development of immunosuppressive protocols that decrease the rate of acute rejection should lower the rate of chronic rejection and improve long-term graft survival.
Acute Disease↗
Augmented enhancement of in vitro production of inflammatory cytokines...
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Bias↗
Venous thromboembolic complications after kidney and kidney-pancreas transplantation: a multivariate analysis.
BACKGROUND: We reviewed the incidence of and risk factors for venous thromboembolic complications in our population of kidney (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients. METHODS: Information was collected retrospectively from a database on 1833 KTx and 276 SPK recipients who underwent transplant surgery between January 1985 and August 1995. RESULTS: The incidence of deep venous thrombosis (DVT) was 6.2% (n= 132), with significantly higher rates after SPK (18.1%) vs. KTx (4.5%) (P < 0.001). The number of DVT episodes was highest in the first month; 17.5% occurred during this time. For KTx recipients, early thrombotic events were more common on the side of the graft (P=0.03); however, after 1 month, no correlation existed between the side of the graft and the side of DVT. For SPK recipients, DVT tended to be more common on the side of the pancreas (57%) vs. the kidney (43%) (P=0.10). By multivariate analysis, risk factors for DVT were: age > 40 years (odds ratio [OR]=2.2, P < 0.001), diabetes mellitus (DM) (OR=2.0, P=0.002), previous DVT (OR=4.4, P=0.001), and SPK transplant (OR=2.8, P < 0.001). Pulmonary embolus (PE) was identified in 44 recipients (incidence, 2.1%) and was fatal in 13 (30%). The incidence was significantly higher in SPK (4.71%) vs. KTx recipients (1.69%) (P < 0.01). The risk of death from PE was 0.5% in KTx recipients and 1.37% in SPK recipients (P=0.08). Risk factors for PE included DM (OR=2.6, P=0.005) and recent DVT (OR=8.9, P=0.0001). CONCLUSIONS: Based on risk and extrapolating from the general surgical literature, our recommendations for prophylaxis against DVT are use of graduated compression stockings for all recipients and, in addition, low-dose heparin for moderate and high-risk recipients (previous DVT, SPK, age > 40 years, DM).
Adult↗
Third-generation cephalosporins and vancomycin as risk factors for postoperative vancomycin-resistant enterococcus infection.
OBJECTIVE: To examine use of third-generation cephalosporins (3GCs) alone and in association with vancomycin hydrochloride as a risk factor for vancomycin-resistant enterococcus (VRE) infection in surgical patients. DESIGN: Case-control retrospective study analyzing antibiotic use in the 30 days preceding culture of VRE or vancomycin-sensitive enterococcus from an infected site. SETTING: A large tertiary care teaching hospital. PATIENTS: Surgical inpatients with VRE infections between September 3, 1993, and January 29, 1997, were matched with patients with vancomycin-sensitive enterococcus infections. Matches were based on surgical procedure, initial infection site, and immunosuppression. Matches were found for 32 of 50 surgical patients with VRE. Twenty matched pairs of patients were recipients of solid organ transplants. MAIN OUTCOME MEASURES: Multivariate logistic regression analysis was done to examine 3GCs and vancomycin as risk factors for VRE infection. Univariate analysis of use of other antibiotic agents and demographic data was also performed. RESULTS: Multivariate analysis showed significant differences in the use of 3GCs both alone and concurrently with vancomycin. Univariate analysis also showed higher use of metronidazole, concurrent vancomycin and metronidazole, concurrent vancomycin and ceftazidime, and all antibiotics combined in patients with VRE infections. CONCLUSIONS: This matched control study showed that use of 3GCs, alone (P=.05) or concurrently with vancomycin (P=.05), was a risk factor for VRE infection in surgical patients. Judicious administration of third-generation antibiotics is warranted in surgical patients with other risk factors for VRE.
Adult↗
Surgical complications requiring early relaparotomy after pancreas transplantation: a multivariate risk factor and economic impact analysis of the cyclosporine era.
OBJECTIVES: To study significant surgical complications requiring early (< or = 3 months posttransplant) relaparotomy (relap) after pancreas transplants, and to develop clinically relevant surgical and peritransplant decision-making guidelines for preventing and managing such complications. SUMMARY BACKGROUND DATA: Pancreas grafts are still associated with the highest surgical complication rate of all routinely transplanted solid organs. However, the impact of surgical complications on morbidity, hospital costs, and graft and patient survival rates has not been analyzed in detail to date. METHODS: We retrospectively studied surgical complications requiring relap in 441 consecutive cadaver, bladder-drained pancreas transplants (54% simultaneous pancreas and kidney [SPK]; 22% pancreas after kidney [PAK]; 24% pancreas transplant alone [PTA]; 37% retransplant). Outcome and hospital charges were analyzed separately for recipients with versus without reoperation. RESULTS: The overall relap rate was 32% (SPK, 36%; PAK, 25%; PTA, 16%; p = 0.04). The most common causes were intraabdominal infection and graft pancreatitis (38%), pancreas graft thrombosis (27%), and anastomotic leak (15%). Perioperative relap mortality was 9%; transplant pancreatectomy was necessary in 57% of all recipients with one or more relaps. The pancreas graft was lost in 80% of recipients with versus 41% without relap (p < 0.0001). Patient survival rates were significantly lower (p < 0.05) for recipients with versus without relap. By multivariate analysis, significant risk factors for graft loss included older donor age (SPK, PAK), retransplant (PAK), relap for infection (SPK, PAK), and relap for leak or bleeding (PAK). For death, risk factors included older recipient age (SPK, PAK),retransplant (SPK, PAK), relap for thrombosis (PAK), relap for infection or leak (SPK), and relap for bleeding (PTA). CONCLUSIONS: Posttransplant surgical complications requiring relap were frequent, resulted in a high rate of pancreas (SPK, PAK, PTA) and kidney (SPK, PAK) graft loss, and had a major economic impact (p = 0.0001). Complications were associated with substantial perioperative mortality and decreased patient survival rates. The focus must therefore shift from graft salvage to preservation of the recipient's life once a pancreas graft-related complication requiring relap occurs. Thus, the threshold for pancreatectomy should be low. In this context, acceptance of older donors and recipients must be reconsidered.
Adolescent↗
The acutely ischemic extremity after kidney transplant: an approach to management.
BACKGROUND: The purpose of this study was to review arterial thromboembolic complications presenting with an acutely ischemic lower extremity after a kidney (KTx) or simultaneous kidney-pancreas transplantation (SPK) and to describe an approach to their management. METHODS: We retrospectively reviewed all such transplantations (a total of 2109) performed between January 1985 and August 1995. We identified 16 recipients (incidence, 0.76%) in whom an acutely ischemic leg developed during the immediate postoperative period (within the first 48 hours). RESULTS: Of the 16 recipients, eight underwent a KTx (incidence, 0.45%) and eight underwent an SPK transplantation (incidence, 2.90%). Median age was 38 years (range, 15 months to 61 years). Thirteen had insulin-dependent diabetes mellitus (IDDM), a significantly higher incidence than in the control group (i.e., transplant recipients without this complication) (p < 0.01). Peripheral vascular disease (PVD) was documented before operation in eight (50%) of the recipients (vs 8.9% in the control group) (p < 0.01). Ten were uremic (on chronic dialysis) before transplantation; six were nonuremic (not on dialysis). Intraoperatively, 14 had moderate to severe atherosclerotic disease affecting the iliac vessels, seven of whom required some manipulation of the artery (either endarterectomy or tacking of the intima) to make it suitable for anastomosis. Heparin was administered systemically during cross clamping to only four. Most of the 16 recipients showed symptoms or signs of arterial occlusion within the first few hours after operation. The most common symptom was pain; the most common physical finding was loss of femoral and distal pulses. Thirteen recipients had moderate to severe ischemia, as judged by physical examination; 15 returned to the operating room for surgical exploration. Eight underwent thrombectomy through an inguinal incision, with successful restoration of flow. Seven underwent exploration through the initial incision because of concern regarding the viability of the transplanted organ; five of them required transplant nephrectomy because of simultaneous thrombosis of the renal artery. No patient needed a bypass procedure to restore flow. Long-term morbidity as a result of the arterial occlusion was related to the severity and length of ischemia. CONCLUSIONS: On the basis of these results, we suggest the following recommendations: (1) all patients should undergo a thorough peripheral vascular examination before and after transplantation; (2) patients at higher risk for arterial thromboembolic complications (e.g., those with significantly diseased vessel at intraoperative examination, nonuremic patients) should receive intraoperative systemic heparin before cross clamping of the artery; and (3) patients with signs or symptoms suggesting arterial occlusion after operation should undergo prompt surgical exploration.
Acute Disease↗
Long-term quality of life after kidney and simultaneous pancreas-kidney transplantation.
We are using a validated questionnaire (SF-36) to annually assess health-related quality of life (QOL) in kidney and pancreas-kidney transplant recipients. The SF-36 consists of eight scales to assess physical functioning, general health, and mental functioning. Norms and 95% confidence intervals (C.I.) have been developed for the US population. At present, 1138 recipients with functioning grafts (520 Type I diabetic; 618 nondiabetic) 1-10 yr post-transplant have completed the questionnaire. Of the recipients, 446 completed the questionnaire once; 632 twice; and 53 three times (305 after 1 yr; 266 after 2 yr; 256 after 3 yr; 206 after 4 yr; 192 after 5 yr; 150 after 6 yr; 130 after 7 yr; 138 after 8 yr; 125 after 9 yr; 92 after 10 yr). For both diabetic and nondiabetic recipients, there was little change in average scores for each scale between years (p = NS). In relation to the US population, average scores for nondiabetics were below the 50th percentile on all 8 scales; for diabetics < 25th percentile on the physical functioning and vitality scales, < 50th percentile on all others. For both diabetic and nondiabetic recipients, average scores were higher than reported norms for patients with CHF, COPD, or depression but were similar to those with Htn or recent MI. Individual scores were then compared with age-matched means (+/- 2 SEMs) (95% C.I.) for the US population. At each year post-transplant, up to 40% of nondiabetic and up to 65% of diabetic recipients had scores below the 95% C.I. on individual scales (particularly the physical functioning and general health scales)--e.g. over 30% nondiabetic and up to 60% diabetic recipients had scores on the physical functioning scales below the 95% C.I. More diabetic recipients (vs. nondiabetics) reported poor QOL on the physical functioning, general health and social functioning scales. There was little difference in the mental health scales. For those with Type I diabetes, a similar percentage of kidney and K/P recipients reported QOL below the 95% C.I. for the age-matched population, except on the GH scale (better QOL for K/P recipients). We conclude that successful transplant recipients report health-related QOL below that of the age-matched general population but similar to those with other chronic diseases. Diabetic and nondiabetic recipients have similar scores on the mental health scales; nondiabetic recipients score better on the general health and physical functioning scales.
Adult↗
Applications of health risk adjustment: what can be learned from experience to date?
Health-based payment is a key component of any strategy for health care reform. This paper summarizes four case studies describing "real-world" applications of health status risk adjustment to determine payments to health plans and providers. For each case study, the context for risk adjustment, the data and methods employed, and the implementation experience are assessed. The experience shows that the tools and methods required for determining health-based payments are available, and in many cases, well developed. They have been applied with success in different settings for different populations. Although many operational issues need to be addressed, obstacles can be overcome and the implementation of health-based payments is a feasible objective.
Actuarial Analysis↗
Solitary pancreas transplantation for nonuremic patients with labile insulin-dependent diabetes mellitus.
BACKGROUND: Simultaneous pancreas-kidney transplantation has become a widely accepted treatment option for selected uremic patients with insulin-dependent diabetes mellitus (IDDM). Patient survival rates at 1 year exceed 90%, and rates of pancreas graft survival, 70%. However, solitary pancreas transplantation for nonuremic patients with IDDM has been controversial because of the less favorable outcome and the need for long-term immunosuppression with its associated morbidity and mortality. METHODS: We studied the outcome of 225 solitary pancreas transplants during three immunosuppressive eras: the precyclosporine (CsA) era (n=83), the CsA era (n=118), and the tacrolimus era (n=24). Only patients with labile IDDM (e.g., hypoglycemic unawareness, insulin reactions, > or = 2 failed attempts at intensified insulin therapy for metabolic control) underwent solitary pancreas transplantation. Using univariate and multivariate analyses, we looked at patient and graft survival, the risk of surgical complications, and native kidney function during these three eras. RESULTS: Pancreas graft survival improved significantly over time: 34% at 1 year after transplantation in the pre-CsA era, 52% in the CsA era, and 80% in the tacrolimus era (P=0.002). Pancreas graft loss due to rejection decreased from 50% at 1 year in the pre-CsA era, to 34% in the CsA era, to 9% in the tacrolimus era (P=0.008). The rate of technical failures (i.e., the risk of surgical complications) decreased from 30% in the pre-CsA era, to 14% in the CsA era, to 0% in the tacrolimus era (P=0.001). Patient survival rates at 1 year have ranged between 88% and 95% in the three eras (P=NS). Matching for at least one antigen on each HLA locus and avoiding HLA-B mismatches significantly decreased the incidence of rejection. The incidence of native kidney failure due to drug-induced toxicity decreased significantly over time, in part because only recipients with pretransplant creatinine clearance > or = 80 ml/min received transplants. CONCLUSIONS: Solitary pancreas transplantation has become a viable alternative for nonuremic patients with labile IDDM. The risks of surgical complications and drug-induced nephrotoxicity have significantly decreased over time. Using tacrolimus as the mainstay immunosuppressant, patient and graft survival rates now no longer trail those of simultaneous pancreas-kidney transplantation.
Adolescent↗
Candida albicans and Escherichia coli are synergistic pathogens during experimental microbial peritonitis.
Candida albicans has been isolated with increasing frequency during intraabdominal infection; yet its role as a pathogen or copathogen remains controversial. A recent experimental study of its effect during polymicrobial peritonitis indicated that it did not enhance mortality when added to an Escherichia coli challenge, but that study used fecal or mucin-based adjuvants which are known to markedly potentiate the lethality of intraperitoneal bacteria. Therefore, we sought to examine the hypothesis that C. albicans and E. coli are synergistic copathogens that act in concert to increase mortality rates in experimental models of polymicrobial peritonitis, irrespective of the presence of growth adjuvant. To test this hypothesis, we assessed the mortality rates of previously healthy Swiss-Webster mice (20 g) that were challenged intraperitoneally (i.p.) with E. coli, C. albicans, or both, in either the presence or the absence of hemoglobin-mucin. In the absence of hemoglobin-mucin, E. coli plus C. albicans resulted in 83.3% mortality (P < 0.02) compared to either E. coli (0%) or C. albicans (0%) alone. In the presence of hemoglobin-mucin, the synergistic effect was not observed, lower numbers of E. coli alone (62.5%), C. albicans alone (75%), or both organisms together (100%, P > 0.05) provoked high lethality. These data demonstrate that in the absence of adjuvant, E. coli plus C. albicans provoked synergistic lethality. However, in the presence of hemoglobin-mucin the synergistic effect was no longer observed. Therefore, this study provides support for the contention that C. albicans is capable of acting as a copathogen during experimental peritonitis, but that this effect may be obscured by the presence of an adjuvant substance that itself markedly potentiates microbial growth.
Adjuvants, Immunologic↗
Immunization with antibodies that mimic LPS protects against gram negative bacterial sepsis.
We developed 9H1.B11, an anti-idiotypic anti-deep core/lipid A (DCLA), murine monoclonal antibody (mAb) that mimics the conserved DCLA region of lipopolysaccharide (LPS). It recognizes an epitope in the variable region of an DCLA mAb, binds to the murine macrophage cell surface, and inhibits LPS-induced macrophage cytokine secretion. We hypothesized that (1) active immunization with mAb 9H1.B11 would be associated with the development of anti-DCLA antibodies and (2) immunization would protect against subsequent gram negative bacterial challenge. Mice were immunized for 8 weeks before intraperitoneal (ip) challenge with Escherichia coli O111:B4 bacteria. Control animals were immunized with an irrelevant IgM antibody 8133 (negative control) or with LPS derived from Salmonella minnesota Re bacteria (positive control). Sera from immunized mice were collected, and titers against the core region of LPS (Re) and against LPS derived from the infecting E. coli strain were determined. Mice immunized with mAb 9H1.B11 developed measurable titers against S. minnesota Re LPS but not against the challenge strain of E. coli. However, immunization with 9H1.B11 on S. minnesota Re LPS protected against subsequent infection due to E. coli O111:B4 (100% survival). The group of mice immunized with IgM 8133 exhibited only 25% survival. The development of an anti-S. minnesota Re LPS titer after immunization with 9H1.B11 provides further evidence that a portion of 9H1.B11 mimics the conserved DCLA region of LPS. We believe that this approach holds considerable promise and plan further studies to define the mechanism by which protective capacity occurs.
Animals↗