Biomedical subjects

D L Dunn

Publications and source records attributed to D L Dunn.

At least 19 recordsLinked to original sources

PubMed2005

Phytoextraction of lead from firing range soil by Vetiver grass.

Phytoextraction techniques utilizing a sterile strain of Vetiver grass (Vetiveria zizanoides) along with soil amendments were evaluated for removing lead and other elements such as Zn, Cu, and Fe from the soil of a 50-year old active firing range at the Savannah River Site (SRS). Lead-contaminated soil (300-4500 ppm/kg) was collected, dried, placed in pots, fertilized, and used as a medium for growing transplanted Vetiver grass plants in a greenhouse. The uptake of metals by the plants was evaluated in response to various fertilization and pre-harvest treatment schemes. Baseline metal concentrations in the soil of all pots were measured prior to planting and when the plants were harvested. Plants grew better when fertilized with Osmocote fertilizer in comparison to plants fertilized with 10-10-10 (NPK) fertilizer. Application of a chelating agent, EDTA, one week prior to harvest significantly increased the amount of lead that was phytoextracted. Lead concentrations of up to 1390-1450 ppm/kg in tissue samples were detected. Maximum Pb levels were observed in root tissues. The addition of non-lethal doses of a slow-release herbicide in combination with EDTA did not appear to further enhance phytoextraction or the translocation of Pb into shoots. The study indicated that the use of Vetiver grass coupled with the use of chelating soil amendments has considerable potential for use as a remedial strategy for lead-contaminated soils such as those associated with firing ranges.

Biotechnology↗

PubMed2005

Mycobacterial infections after kidney transplant.

We looked at mycobacterial infections occurring after a kidney transplant to determine incidence, risk factors, and outcomes. Of 3921 kidney transplants performed between 1984 and 2002, 18 (0.45%) (10 men, eight women; 11 cadaveric donor, seven living donor graft) were identified as having mycobacterial infection at some time posttransplant. Mean age at transplant was 38.3 years. Racial background was: Caucasian (n = 12), African-American (n = 2), Native Indian (n = 2), Hispanic (n = 1), and Middle Eastern (n = 1). The majority had a kidney alone (n = 14). Four recipients had simultaneous transplant of a second organ: pancreas (n = 2), islets (n = 1), and liver (n = 1). None of the 18 recipients had documented mycobacterial infection pretransplant. One recipient had a positive Mantoux test at the time of transplant and then developed pulmonary tuberculosis 4 months posttransplant; the remaining 17 patients had either negative (n = 10) or unavailable (n = 7) pretransplant Mantoux results. Mean time to infection was 3.2 years (range 1 week to 12 years). The most common site of infection was respiratory (n = 8). Other sites included musculoskeletal (n = 4), skin (n = 3), gyn (n = 1), and other (n = 2). Only three of the infections were with mycobacterial tuberculi; the others were with avium (n = 5), chelonae (n = 2), or other nontuberculous mycobacteria. Risk factors included previous TB exposure, occupational exposure, or accidental soft tissue injury. Soft tissue infections often presented as chronic unhealed wounds and required extensive surgical debridements. With mean follow-up of 12.5 years since transplant and 9.2 years since infection, 13 of the recipients are alive and well; causes of death included cardiovascular (n = 3) and sepsis (n = 2).

Adult↗

PubMed2005

Fungal infections in transplant recipients receiving alemtuzumab.

Recently, we have used an anti-T-cell agent, alemtuzumab, as induction or conversion therapy to achieve a calcineurin (CNI) and steroid-free immunosuppressive regimen. We identified recipients who developed systemic fungal infections after the initiation of alemtuzumab and looked at their outcomes. The study population consisted of all pancreas transplant recipients who received alemtuzumab. Only invasive fungal infections were included in the analysis (eg, fungemia, meningitis, or pneumonia; fungal urinary tract infections were excluded). The organism was confirmed by culture, histopathology, or latex antigen test. Between February 2003 and February 2004, a total of 121 pancreas transplant recipients received alemtuzumab-56 as part of induction, and 65 as part of conversion. Of these, 8 (6.6%) developed an invasive fungal infection; 2 (3.6%) recipients as part of induction therapy and 6 (9.2%) as part of conversion therapy. Mean recipient age was 42.1 years. The mean length of time from alemtuzumab administration (first dose) to the diagnosis of the fungal infection was 115.9 days (range 5 to 318). The organisms identified initially were: Cryptococcus, Histoplasma, Aspergillus, and Candida. Overall, 3 (38%) of the eight patients died during ongoing treatment of their fungal infection: two from sepsis, one due to myocardial infarction. The other five recipients were treated successfully and have functioning grafts. The initial therapeutic agents used included: amphotericin B/liposomal AMB (n = 6), voriconazole (n = 3), capsofungin (n = 2), and fluconazole (n = 1). The use of alemtuzumab as induction or conversion therapy in pancreas transplant recipients may predispose patients to the development of systemic fungal infections. It would be important to determine what the most appropriate prophylaxis regimen would be for these patients.

Alemtuzumab↗

PubMed2003

A deeply invasive Phoma species infection in a renal transplant recipient.

Phoma sp, a fungus routinely isolated from the soil and a known plant pathogen, was found to be the cause of an aggressive, deep compartment hand infection in a renal transplant recipient. Previous reports have described minimally invasive Phoma sp infections with isolates recovered from the skin or subcutaneous tissue. This case, however, is the first reported in which Phoma sp was found to be both aggressive and deeply invasive. Histologic sections obtained from the synovium of the fourth and fifth dorsal hand compartments revealed invasive hyphal elements. Detailed examination with Grocott-Gomori methenamine-silver staining revealed branching filaments and pycnidia. A Phoma sp was isolated from culture after 2 weeks of incubation. Antifungal agent sensitivity testing found the organism to be sensitive to amphotericin B but resistant to both fluconazole and 5-flucytosine. Treatment required surgical debridement and the use of prolonged systemic amphotericin B therapy in order to effect cure. This is a unique case of a deeply invasive Phoma sp infection, indicating that such processes are not strictly indolent as previously reported.

Amphotericin B↗

PubMed2001

Rapid discontinuation of steroids in living donor kidney transplantation: a pilot study.

UNLABELLED: Steroids are associated with significant postoperative complications (hypertension, cosmetic changes, bone loss, hyperlipidemia, diabetes, and cataracts). Most develop early; in addition, late post-transplant steroid withdrawal in kidney transplant recipients has been associated with increased acute rejection (AR). To obviate these problems, we studied outcome of a protocol of rapid discontinuation of prednisone (RDS) (steroids stopped on POD6). Between November 1, 1999 and October 31, 2000, 51 adult living donor (LD) first transplant recipients (2 HLA-id, 28 non-id relative, 21 LURD) were immunosuppressed with thymoglobulin (1.25 mg/kg intraoperatively and then qdx4); prednisone (P) (500 mg methylprednisolone intraoperatively, 1 mg/kg x 1 day, 0.5 mg/kg x 2 days, 0.25 mg/kg x 2 days, then d/c); MMF, 1 g b.i.d.; and CSA, 4 mg/kg b.i.d. adjusted to achieve levels of 150-200 ng/mL (by HPLC). Exclusion criteria were delayed graft function or primary disease requiring P. Minimum follow-up was 5.5 months (range 5.5 to 17.5 months). Outcome was compared vs. previous cohorts of LD recipients immunosuppressed with P/AZA/CSA (n = 171) or P/MMF/CSA (n = 43) (both without antibody induction). RESULTS: For the RDS group, average CSA level (+/- S.E.) at 3 and 6 months was 190 +/- 12 and 180 +/- 9; avg. MMF dose, 1.7 +/- 0.1 g and 1.7 +/- 0.1 g. There was no significant difference in 6- and 12-month actuarial patient survival, graft survival and rejection-free graft survival between recipients on the RDS protocol vs. historical controls. For RDS recipients, actuarial 6- and 12-month rejection-free graft survival was 87%. Of the 51 RDS recipients, five (10%) have had AR (at 20 days, 1 month, 3 months, 3 months, and 3.5 months post-transplant). After treatment, all five were maintained on 5 mg P; there have been no second AR episodes. Two additional recipients were started on 5 mg P due to low white blood count (WBC) and low/no MMF. Of the 51 grafts, one has failed (death with function). Average serum Cr level (+/- S.E.) at 3 and 6 months for RDS recipients was 1.7 +/- 0.5 (NS vs. historical controls). CONCLUSION: For low-risk LD recipients, a kidney transplant with an RDS protocol does not increase risk of AR or graft loss. Future studies will need to be done to assess AR rates with an RDS protocol in cadaver transplant recipients and in recipients with delayed graft function.

Azathioprine↗

PubMed2001

Accelerated internalization and detoxification of endotoxin by anti-lipopolysaccharide antibody is an Fc receptor--mediated process.

BACKGROUND: Interaction between lipopolysaccharide (LPS), LPS-binding protein, and the CD14 receptor at the surface of LPS-responsive cells results in inflammatory cytokine release and internalization and detoxification of LPS. Monoclonal antibodies (mAbs) raised against the deep-core lipid A or the O-linked polysaccharide moieties of LPS accelerate internalization and detoxification of LPS without stimulating cytokine release. This study was conducted to test the hypothesis that the antibody-mediated internalization of LPS is an Fc receptor (FcR)--mediated process. METHODS: Fluoroisothiocyanate (FITC)-conjugated Escherichia coli O111:B4 LPS was incubated with RAW 264.7 cells and allowed to internalize for 2 hours in the presence and absence of anti-LPS, anti-CD14, and isotype control mAbs, and Fab fragments from the anti-CD14, anti--Fc receptor, and control mAbs. Tumor necrosis factor--alpha (TNF-alpha) release was measured by WEHI 164 cell bioassay. FITC-LPS uptake was measured by flow cytometry. Statistical analysis was by analysis of variance and Fisher exact test. RESULTS: Addition of anti-LPS antibodies resulted in a 30- to 40-fold acceleration of LPS internalization (P <.01) in agreement with previous studies. This increase was blunted by anti-CD14 and also by isotype control holo-antibody (P <.01), but not by Fab fragments from anti-CD14 or isotype control antibody. Both anti-FcR antibodies and Fab fragments blocked anti-LPS antibody--stimulated uptake of FITC-LPS. Both intact anti-CD14 holo-antibody and Fab fragments blocked TNF-alpha release (P <.01). CONCLUSIONS: Clearance and detoxification of LPS are thought to be essential to the host response to endotoxin. It has been shown that antibodies to LPS accelerate its internalization by monocytic cell lines without increasing the elaboration of cytokines. We found that specific blockade of CD14 by Fab fragments could block TNF-alpha release but not alter the accelerated internalization of LPS produced by anti-LPS antibodies. In contrast, a nonspecific blockade of internalization was produced by competing antibody, which suggests a mechanistic role for the FcR. Specific blockade of FcR by either holo-antibody or Fab fragments blocked accelerated internalization, which confirms a FcR mechanism. We conclude that the accelerated internalization of LPS produced by anti-LPS antibody is an Fc receptor--mediated process. These results have significance for the development of adjuvant immunotherapy for gram-negative bacterial sepsis.

Animals↗

PubMed2001

Hazardous crossing: immunosuppression and nosocomial infections in solid organ transplant recipients.

BACKGROUND: During the past decade, ever-increasing numbers of patients have undergone renal, pancreatic, small bowel, hepatic, cardiac, or lung transplantation as therapy for various types of renal disease requiring dialytic therapy. Indications for solid organ transplantation include type I and, rarely, type II diabetes mellitus; hyperalimentation-dependent short gut syndrome; and formerly fatal liver, cardiac, or pulmonary failure. Significant improvements in patient and allograft survival have been observed in all categories. Unfortunately, despite such improved results, the risks of infection related to immunosuppression continue to be substantial. METHODS: Review of pertinent studies from the English literature. RESULTS: Suppression of host defenses by exogenous immunosuppressive agents renders patients susceptible to invasion by either resident or environmental bacterial, fungal, viral, and protozoal microbes or parasites. In such patients, invasion of organisms that produce mild infection in nonimmunosuppressed individuals can produce severe, lethal disease. Moreover, even low-virulence microbes may invade, proliferate, and cause disease in the immunosuppressed host; such organisms are referred to as "opportunistic" pathogens when they cause disease under these conditions. CONCLUSION: Advances in the field of transplantation have been substantial, particularly in the regulation of therapeutic immunosuppression, in prophylactic measures to prevent infection, and in more effective diagnosis and treatment modalities.

Cross Infection↗

PubMed2001

Lessons learned from more than 1,000 pancreas transplants at a single institution.

OBJECTIVE: To determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution. SUMMARY BACKGROUND DATA: Insulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants. METHODS: From December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n = 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n = 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA. RESULTS: Patient and primary cadaver pancreas graft functional (insulin-independence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61) versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n = 30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic secondary complications were ameliorated in some recipients, and quality of life studies showed significant gains after the transplant in all recipient categories. CONCLUSIONS: Patient and graft survival rates have significantly improved over time as surgical techniques and immunosuppressive protocols have evolved. Eventually, islet transplants will replace pancreas transplants for suitable candidates, but currently pancreas transplants can be applied and should be an option at all stages of diabetes. Early transplants are preferable for labile diabetes, but even patients with advanced complications can benefit.

Adolescent↗

PubMed2001

2,500 living donor kidney transplants: a single-center experience.

OBJECTIVE: To review a single center's experience and outcome with living donor transplants. SUMMARY BACKGROUND DATA: Outcome after living donor transplants is better than after cadaver donor transplants. Since the inception of the authors' program, they have performed 2,540 living donor transplants. For the most recent cohort of recipients, improvements in patient care and immunosuppressive protocols have improved outcome. In this review, the authors analyzed outcome in relation to protocol. METHODS: The authors studied patient and graft survival by decade. For those transplanted in the 1990s, the impact of immunosuppressive protocol, donor source, diabetes, and preemptive transplantation was analyzed. The incidence of rejection, posttransplant steroid-related complications, and return to work was determined. Finally, multivariate analysis was used to study risk factors for worse 1-year graft survival and, for those with graft function at 1 year, to study risk factors for worse long-term survival. RESULTS: For each decade since 1960, outcome has improved after living donor transplants. Compared with patients transplanted in the 1960s, those transplanted in the 1990s have better 8-year actuarial patient and graft survival rates. Death with function and chronic rejection have continued to be a major cause of graft loss, whereas acute rejection has become a rare cause of graft loss. Cardiovascular deaths have become a more predominant cause of patient death; infection has decreased. Donor source (e.g., ideally HLA-identical sibling) continues to be important. For living donor transplants, rejection and graft survival rates are related to donor source. The authors show that patients who had preemptive transplants or less than 1 year of dialysis have better 5-year graft survival and more frequently return to full-time employment. Readmission and complications remain problems; of patients transplanted in the 1990s, only 36% never required readmission. Similarly, steroid-related complications remain common. The authors' multivariate analysis shows that the major risk factor for worse 1-year graft survival was delayed graft function. For recipients with 1-year graft survival, risk factors for worse long-term outcome were pretransplant smoking, pretransplant peripheral vascular disease, pretransplant dialysis for more than 1 year, one or more acute rejection episodes, and donor age older than 55. CONCLUSIONS: These data show that the outcome of living donor transplants has continued to improve. However, for living donors, donor source affects outcome. The authors also identify other major risk factors affecting both short- and long-term outcome.

Adolescent↗

PubMed2001

Binding specificity of polymyxin B, BPI, LALF, and anti-deep core/lipid a monoclonal antibody to lipopolysaccharide partial structures.

The deep core/lipid A (DCLA) region of gram-negative bacterial lipopolysaccharide (LPS) is common to most gram-negative pathogens and contains anionic phosphoryl groups plus numerous acyl chains as part of the toxic lipid A moiety. Several disparate agents that antagonize the effects of LPS exhibit extensive physicochemical similarities (hydrophobicity, cationic charge) within their binding domains. It is presumed that binding to the DCLA region by each of these antagonists-cross-reactive anti-LPS monoclonal antibodies (mAbs), polymyxin B (PmB), plus bactericidal permeability-increasing protein (BPI) and Limulus anti-LPS factor (LALF)-may be related to these properties. Therefore, we hypothesized that in addition to secondary and tertiary protein conformation, electrostatic interactions involving the negatively charged phosphoryl groups, hydrophobic interactions involving the acyl chains of lipid A, or both might be important factors that promote LPS antagonism. Binding of PmB, BPI, LALF, or anti-DCLA mAb 1B6 to Salmonella minnesota monophosphoryl lipid A (MPLA), diphosphoryl lipid A (DPLA), and Salmonella minnesota Re (which possess a common structural moiety, but vary considerably in structure and charge) was examined. Highly phosphorylated DNA and bovine serum albumin served as unrelated structural controls. BPI bound MPLA, which is hydrophobic and minimally charged, while mAb 1B6 bound anionic DNA; neither PmB nor LALF were reactive with MPLA or DNA. We surmised that hydrophobic interactions play a role in BPI binding to LPS, and although electrostatic interactions appear to be important for binding of mAb 1B6 to DCLA, they may not contribute to as great an extent for PmB, BPI, or LALF. Thus our data support the contention that the contribution of these specific physicochemical factors varies among endotoxin antagonists.

Amino Acid Sequence↗

PubMed2000

Immunologic and nonimmunologic factors: different risks for cadaver and living donor transplantation.

BACKGROUND: There is a debate about the relative contribution of immunologic (rejection) and nonimmunologic (limited nephron mass) factors in long-term graft survival. METHODS: Using multivariate analysis, we studied the association of the following variables with outcome: delayed graft function (DGF), acute rejection, recipient race (black vs. nonblack), donor age (<50 vs. > or =50), donor race, and donor and recipient gender. Because of the association between DGF and rejection, recipients were grouped as follows: DGF, rejection; DGF, no rejection; no DGF, rejection; no DGF, no rejection. Data were analyzed on 1199 first kidney transplants in adults (752 living donor, 447 cadaver donor) done between January 1, 1985 and December 31, 1996. Two analyses were done: first, all transplants; second, only those with > or =1 year survival. For both, there was no difference in risk factors if death with function was or was not censored. RESULTS: For all cadaver transplant recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50. For living donor recipients, only acute rejection was a risk factor. When only 1-year graft survivors were considered, risk factors were the same: for cadaver recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50; for living donor recipients the risk factor was rejection. CONCLUSION: We found immunologic factors (rejection with or without DGF) to be significant in both living donor and cadaver donor transplants. Nonim. munologic factors (donor age, recipient race) were significant only in cadaver donor transplants.

Acute Disease↗

PubMed2000

Should I accept this kidney?

BACKGROUND: Transplant candidates frequently ask whether they should, based on information available at the time, accept a cadaver kidney or wait for a potentially better one. METHODS: We analyzed 937 first and second cadaver transplants done between January 1, 1984 and December 31, 1997 to determine if information available at the time an offer is made could be used to predict long-term graft survival. RESULTS: By Cox regression, risk factors for worse long-term graft survival were older donor age, cardiovascular or cerebrovascular cause of donor death, and delayed graft function (DGF). HLA-ABDR mismatch was marginally significant. Whether DGF will occur is not known at the time of an offer, but risk factors can be determined; we found these to be older donor age and > 10% panel-reactive antibodies (PRA) at transplantation (by Cox regression). Using these variables (PRA, ABDR mismatch, donor age, and donor cause of death) known at the time of an offer, we calculated the relative risk of worse long-term graft survival for each subgroup (Table 3 in manuscript). In general, older age and donor death from cardiovascular or cerebrovascular disease were associated with worse outcome. Kidneys from donors of < 50 yr had the best outcome, irrespective of match. CONCLUSION: The data provided can be used to help guide patients as to whether they are better off accepting an offered kidney or waiting for a potentially better one. If an offer is declined, the next kidney may have a potentially worse outcome.

Adolescent↗

PubMed2000

Bactericidal and endotoxin neutralizing activity of a peptide derived from Limulus antilipopolysaccharide factor.

BACKGROUND: Release of lipopolysaccharide (endotoxin, LPS) is a critical inciting event in the development of sepsis syndrome due to gram-negative bacteria, and mortality associated with this entity remains approximately 40%. Limulus anti-LPS factor (LALF) is a naturally occurring horseshoe crab derived protein that, unlike antibiotics, is both bactericidal for gram-negative bacteria and capable of neutralizing LPS. We hypothesized that a peptide derived from the active domain of LALF (LALF #28-54) would exhibit potent biologic activity similar to that of LALF itself and could potentially be useful as a therapeutic agent. METHODS: The effects of LALF, synthetic peptide LALF #28-54, polymyxin B (PmB), and a biologically inactive synthetic peptide were examined in several models. In vitro bactericidal activity was determined against Pseudomonas aeruginosa, and LPS-neutralizing capacity was determined via inhibition of LPS-induced tumor necrosis factor-alpha (TNF-alpha) secretion by RAW 264.7 cells. In vivo biologic activity was determined via pretreatment following which P aeruginosa endotoxemia or bacteremia was induced; serum TNF-alpha levels, bacterial clearance, and survival were assessed. RESULTS: LALF and LALF #28-54 exhibited potent in vitro bactericidal and LPS-neutralizing activity comparable to PmB (P <.01). However, although LALF #28-54 diminished systemic TNF-alpha production and aided bacterial clearance similar to that observed for LALF (P <.01), it did not provide significant protective capacity (P >.1). CONCLUSIONS: These data demonstrate that peptide LALF #28-54 retained the LPS-neutralizing and bactericidal biologic activity of LALF but failed to protect during overwhelming P aeruginosa bacteremia, perhaps due to short serum half-life.

Amino Acid Sequence↗

PubMed2000

Salvage therapy of open, infected surgical wounds: a retrospective review using Techni-Care.

OBJECTIVE: To determine outcome of infected surgical wounds treated with 3% para-chloro-meta-xylenol + 3% phospholipid PTC [PCMX-PL] (Techni-Care). DESIGN: Retrospective review of patient records. SETTING: University hospital. PATIENTS: Thirty consecutively treated patients (sixteen male, fourteen female) who had developed open infected wounds (twenty-one abdominal [seventy percent], nine extremity [thirty percent]). Mean patient age was 50.1 years. All wounds were treated with commonly practiced wound care techniques (e.g., debridement, frequent dressing changes using saline or topical antibiotics, and, in most cases, parenteral antibiotics) for an extended period of time prior to intervention (mean = 35 days). INTERVENTIONS: PCMX-PL, a topical microbicide, was used as adjunctive therapy. Eight outcome parameters were analyzed: (1) patient morbidity and mortality; (2) wound healing; (3) number of debridements; (4) wound culture results; (5) leukocytosis (peripheral white blood cell count > 10,000 cells/microl); (6) number of febrile days (temperature > 101 degrees F); (7) length of hospital stay; and (8) number of days of intensive care. RESULTS: No treatment failures or adverse reactions to PCMX-PL were seen. Twenty (sixty-seven percent) wounds were healed or had been successfully closed while ten (thirty-three percent) were granulating well at sixty-day follow-up. The number of debridements, positive wound cultures, white-blood-cells, and febrile days decreased after PCMX-PL treatment began. CONCLUSIONS: Despite severe underlying diseases, all patients were discharged from the hospital with closed or healing wounds. We recommend treatment with PCMX-PL as an adjunctive therapy for infected wounds particularly when standard care measures have failed.

Adult↗

PubMed2000

Prevention and treatment of multiple organ dysfunction syndrome: lessons learned and future prospects.

Gram-negative bacteria commonly cause serious infections in hospitalized patients, and those that lead to bacteremic episodes and sepsis syndrome are associated with the highest mortality rate. Sepsis syndrome frequently progresses to multisystem organ dysfunction and failure, with as many as 400,000 cases occurring annually. Unfortunately, the associated mortality rate remains about 40%. Lipopolysaccharide (LPS, endotoxin), an integral component of the gram-negative bacterial outer membrane, plays a critical role in the pathophysiology of this lethal disease process. It is capable of interacting with host macrophages, a process that leads to the secretion of an increasingly well-characterized array of macrophage cytokines. Several different classes of compounds that bind directly to LPS and thereby neutralize its effects are being examined. These consist of anti-LPS monoclonal antibodies (mAbs), naturally occurring proteins and their derivatives (e.g., bactericidal/permeability-increasing protein [BPI], Limulus anti-LPS factor [LALF]), and certain antibiotics (polymyxin B, taurolidine). The molecular biology of BPI, LALF, and LPS binding protein (LBP, which augments the host response to LPS) is of considerable interest, as each demonstrates considerable genetic sequence homology. Although two anti-LPS monoclonal antibodies (HA-1A, E5) did not demonstrate efficacy during sepsis syndrome, information obtained from these clinical trials provided investigators with the ability to better understand this disease process. However, a detailed understanding of the biology of endotoxin antagonism is beginning to emerge, and the application of this knowledge in the clinical setting provides hope that it may be possible to reduce the mortality of sepsis syndrome caused by these microorganisms to a statistic well below the current 40%.

Gram-Negative Bacterial Infections↗

PubMed2000

Diagnosis and treatment of opportunistic infections in immunocompromised surgical patients.

The advent of successful therapy for patients who suffer many types of organ dysfunction and failure, malignancies, and acquired immunodeficiency syndrome has led to the concurrent threat of infection due to a wide array of pathogens, particularly opportunistic microbes that rarely cause disease under routine circumstances. Among patients who are subjected to extreme degrees of immunosuppression, almost any type of bacterial, fungal, viral, protozoal, or parasitic organism can exhibit pathogenic potential and lead to devastating consequences for the host. Immunosuppressive drug therapy for the purpose of organ allograft maintenance, cancer chemotherapy, or the human immunodeficiency virus exerts potent effects upon cellular immunity. Therefore, although these groups of patients are more susceptible to all types of infectious disease processes, infections due to those pathogens that require a component of cellular immunity for their eradication, such as fungi and viruses, occur at a higher frequency than that observed among normal individuals. Of critical importance, all types of infections are associated with higher rates of morbidity and mortality in immunosuppressed patients. Currently, improved diagnostic techniques and new treatment modalities have rendered many serious infections, for which suitable therapy previously did not exist, amenable to treatment. Because of the large number of immunosuppressed patients who now lead highly productive lives, it is important for the surgical practitioner to become familiar with the modalities currently available to precisely diagnose and effectively treat opportunistic infections in immunocompromised surgical patients.

Bacterial Infections↗

PubMed2000

5,000 kidney transplants--a single-center experience.

Between 6/1963 and 12/1998, 5,069 kidney transplants were done at the University of Minnesota. Of these, about half have been living donor, half cadaver. The majority (83%) have been primary transplants. Recipients were grouped in 6 eras based on changes in our immunosuppressive protocols--6/63-12/67 (n = 98); 1/68-7/79 (n = 1,188); 8/79-6/84 (n = 789); 7/84-9/90 (n = 1,006); 10/90-12/95 (n = 1,050; 1/96-12/98 (n = 718)--and their outcomes were compared. Recent eras contained a higher proportion of recipients aged > 50. Since the inception of the program, there has been a steady improvement in actuarial patient survival, graft survival, and death-censored graft survival. Short-term outcome for primary and retransplant recipients has been similar; however, long-term outcome seems worse for retransplant recipients. Importantly, acute rejection and infectious death have become rare causes of graft loss. Chronic rejection and death with function (most often due to a cardiovascular event) have become the predominant causes of graft loss. Recent changes in immunosuppressive protocols (Era VI) have included more aggressive attempts to maintain CsA levels > 150 ng/ml (by HPLC) in the first 3 months and the substitution of mycophenolate mofetil for azathioprine. As a result, the incidence of acute and chronic rejection has decreased and graft survival has improved.

Adolescent↗

PubMed1999

Association between cytomegalovirus disease and chronic rejection in kidney transplant recipients.

BACKGROUND: It has long been suggested that cytomegalovirus (CMV) disease plays a role in the pathogenesis of chronic rejection (CR). However, its role has been difficult to prove, given the strong association between acute rejection and CMV, and the even stronger association between acute rejection and CR. To try to isolate the relative contribution of CMV infection in the pathogenesis of CR, we used multivariate techniques to examine risk factors for CR, including CMV disease. METHODS: Our study population consisted of adult recipients of a first kidney graft who underwent transplantation at a single center between 1/1/85 and 6/30/97 (n = 1339). RESULTS: Multivariate analysis using time to CR as the dependent variable demonstrated acute rejection to be the strongest risk factor (relative risk [RR] = 17.8, P = 0.0001), followed by older donor age (RR = 1.46, P = 0.01). The presence of CMV disease showed a trend toward increased risk for CR (RR = 1.30, P = 0.10), although the association was not as strong as with the other two variables. Comparing only those recipients with acute rejection and CMV disease versus those with acute rejection but no CMV disease, the relative risk of developing CR was 1.37 times higher in the former group. Recipients with acute rejection and CMV developed CR sooner and with a higher incidence versus those with acute rejection but no CMV (P = 0.002). It is interesting, however, that CMV disease was only a risk factor for CR in the presence of acute rejection. Recipients with no acute rejection and CMV disease did not have a higher incidence of CR versus those with no acute rejection and no CMV (P = NS). CONCLUSION: CMV disease seems to play some role in the pathogenesis of CR but only in the presence of acute rejection. Reasons may include (i) the inability to adequately treat acute rejection due to the presence of CMV disease or (ii) the increased virulence of latent CMV virus in recipients being treated for acute rejection. Our data may suggest a role for more aggressive prophylaxis against CMV disease, especially at the time of treatment for acute rejection.

Acute Disease↗