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P W Nelson

Publications and source records attributed to P W Nelson.

At least 19 recordsLinked to original sources
PubMed1995

Antifungal susceptibility testing of isolates from a randomized, multicenter trial of fluconazole versus amphotericin B as treatment of nonneutropenic patients with candidemia. NIAID Mycoses Study Group and the Candidemia Study Group.

The antifungal susceptibilities of 232 pathogenic blood stream Candida isolates collected during a recently completed trial comparing fluconazole (400 mg/day) with amphotericin B (0.5 mg/kg of body weight per day) as treatment for candidemia in the nonneutropenic patient were determined both by the National committee for Clinical Laboratory Standards M27-P macrobroth methodology and by a less cumbersome broth microdilution methodology. For amphotericin B, M27-P yielded a very narrow range of MICs (0.125 to 1 microgram/ml) and there were no susceptibility differences among species. For fluconazole, a broad range of MICs were seen (0.125 to > 64 micrograms/ml), with characteristic MICs seen for each species in the rank order Candida albicans < C. parapsilosis approximately equal to C. lusitaniae < C. glabrata approximately equal to C. krusei approximately equal to C. lipolytica. The MIC distribution for C. tropicalis was bimodal and could not be ranked. Both microdilution MICs were within one tube dilution of the M27-P MIC for > 90% of isolates with amphotericin B and for > or = 77% of isolates with fluconazole. For both methods, elevated MICs did not predict treatment failure. In the case of amphotericin B, the MIC range was too narrow to permit identification of resistant isolates. In the case of fluconazole, MICs for isolates associated with failure to clear the bloodstream consistently were equivalent to the median MIC for the given species. Successful courses of therapy were seen with four isolates from four patients despite MICs of > or = 32 micrograms/ml. As MICs obtained by M27-P and similar methods correlate with responsiveness to fluconazole therapy in animal models and in AIDS patients with oropharyngeal candidiasis, the lack of correlation in this setting suggests that the MICs for these isolates are at or below the relevant fluconazole breakpoint for this dose of fluconazole and patient setting and that host factors such as failure to exchange intravenous catheters were more important than MIC in predicting outcome.

Amphotericin B↗
PubMed1992

Current experience with renal transplantation across the ABO barrier.

Solid organ transplantation has traditionally been governed by the rules of blood group compatibility. Thus, it has been demonstrated that crossing the ABO blood group barrier generally results in hyperacute rejection. However, the A2 subtype of the blood group A is a weaker antigen. Under certain circumstances, organs from donors with blood group A2 can be transplanted across the ABO blood group barrier into recipients of O or B blood type. Since 1986, 33 patients including 24 blood group O and 9 blood group B patients received A2 (30) or A2B (3) donor kidneys. Both cadaver donor (31) and living-related grafts (2) have been undertaken. The mean follow-up since transplantation for the 21 patients with functioning grafts is 36 months, with a 67.2% current graft survival. Immunosuppression for these transplants consisted of azathioprine, prednisone, and cyclosporine, often in combination with prophylactic OKT3 or antilymphocyte globulin as protocol dictated. Special immunosuppressive protocols such as splenectomy or plasmapheresis were not used. The serum of the potential recipient was analyzed for immunoglobulin G (IgG) and immunoglobulin M (IgM) forms of antibody against A1 and A2 red blood cells. There is a strong correlation between a low (less than or equal to 1:8) anti-A1 IgG titer and both early and long-term graft function. Recipients with an IgG titer greater than 1:8 in the pretransplant serum had a much higher incidence of early graft failure. We no longer recommend transplantation of A2 kidneys into O or B recipients with a pretransplant titer of greater than 1:8 but found that recipients with low titers have graft function rates essentially equal to those of ABO-compatible patients. Patients with blood group B have, over time, lower anti-A IgG titers than do blood group O patients. In addition, the graft survival among blood group B patients is 89% compared with 58% among group O recipients. This may be due to the generally low titers found in blood group B recipients. Since instituting a policy in 1988 of not transplanting the kidney when the anti-A IgG titer is greater than 1:8, the survival in O patients is 88%. We recommend the screening of all organ donors with blood group A for the A2 subgroup and believe that transplantation can be safely and successfully performed in certain patients with blood group O or B.(ABSTRACT TRUNCATED AT 400 WORDS)

ABO Blood-Group System↗
PubMed1992

A prospective evaluation of plasma-TFE and expanded PTFE grafts for routine and early use as vascular access during hemodialysis.

The use of prosthetic grafts as vascular access for chronic hemodialysis is frequently necessary in patients with end-stage renal disease. Most commonly, expanded polytetrafluoroethylene (e-PTFE) has been employed because of ease of handling, tissue inertness, and acceptable long-term patency. Delay in use to allow for tissue ingrowth, however, has often required placement of temporary access devices. The authors have undertaken evaluation of a new material, plasma polymerized woven dacron Plasma-TFE, in a prospective randomized trial (Plasma-TFE VA) to compare clinical behavior against e-PTFE grafts, and we have used the Plasma-TFE grafts in an additional group of patients (Plasma-TFE AVA) as early access (within 1 week of implantation). Twenty-one Plasma-TFE grafts were implanted in 19 patients and 19 e-PTFE grafts were implanted in 17 patients in a prospective randomized fashion. Additionally, 31 Plasma-TFE grafts were implanted in 31 nonrandomized patients for early access. Primary patency rates in Plasma-TFE VA and e-PTFE grafts were equivalent at 12 months (0.471 and 0.556). When Plasma-TFE AVA primary patency was included (0.621), comparisons were not statistically significant (p = 0.50). Similarly, secondary patency rates among the three groups did not differ (cumulative proportion patent at 12 months: Plasma-TFE VA 0.403, e-PTFE 0.658, Plasma-TFE AVA 0.510). In considering after-revision patency after graft thrombosis, however, the Plasma-TFE grafts (both VA and AVA) performed significantly more poorly (p = 0.027) than e-PTFE grafts. Incidence of graft infection, wound infection, arm edema, hematoma from use, and occurrence of distal limb ischemia between Plasma-TFE (VA and AVA) and e-PTFE did not differ statistically. The authors conclude that Plasma-TFE compares favorably to e-PTFE with respect to primary and secondary patency and nonthrombotic complications, even with early use. Plasma-TFE does not perform as well as e-PTFE, however, after graft thrombosis.

Blood Vessel Prosthesis↗
PubMed1991

High incidence of cardiopulmonary complications associated with implantation of adrenal medullary tissue into the caudate nucleus in patients with advanced neurologic disease.

OBJECTIVE: The purpose of our study was to examine the cardiopulmonary complications of a group of patients who had undergone implantation of adrenal medullary tissue into the caudate nucleus for treatment of neurologic disease. DESIGN: Prospective study with partially matched historical controls. SETTING: Tertiary care community medical center. PATIENTS AND METHODS: Seven patients with advanced Parkinson's disease and three patients with progressive supranuclear palsy underwent implantation of adrenal medullary tissue into the caudate nucleus. These patients were compared with respect to their cardiopulmonary complications with a control group who had undergone craniotomy and then compared with a control group who had undergone only abdominal surgery. RESULTS: In the study group, six patients developed major postoperative complications including development of large pleural effusions, lobar atelectasis, pneumonia, upper airway obstruction, and cardiac arrest. Three patients had minor complications including development of small pleural effusions, subsegmental atelectasis, purulent bronchitis, mild congestive heart failure, and atrial flutter/fibrillation. One patient had an unremarkable postoperative course. The first control group, whose only surgery was a craniotomy, had only one major complication. The second control group, the abdominal surgery control group, had one major and five minor complications. CONCLUSION: The particular neurologic disease, its severity, and the type of surgery performed appear to be causative factors in the high incidence of complications in the study group.

Adrenal Medulla↗
PubMed1990

Elective conversion from cyclosporine to azathioprine in sensitized patients following cadaveric renal transplantation.

The safety of conversion from cyclosporine to azathioprine following renal transplantation in patients generally considered to be at immunologic risk for allograft loss has not been established. We examined a group of 59 patients who underwent cadaveric renal transplantation and elective conversion from cyclosporine to azathioprine 8.3 +/- 3.8 months following transplantation. Forty-three of these patients received a first transplant and had panel-reactive antibodies (PRA) less than 40% (unsensitized). Sixteen patients received at least their second allograft or had PRA of 40% or more (sensitized). Average follow-up was 17.9 +/- 8.2 months. Nine patients (15%) failed conversion as manifested by the need to restart cyclosporine 1 to 10 months following conversion. All were in the unsensitized group. Of those successfully converted, there were six allograft failures, two from patient death, one from acute rejection, one from recurrent diabetic nephropathy, and two from patient noncompliance. All were in the unsensitized group, although the difference from the sensitized group was not statistically significant (P = 0.051). There were three rejection episodes, all successfully reversed, in the sensitized group and six rejection episodes in the unsensitized group, five of which were reversed. Overall renal function improved in both groups as shown by a significant decrease in serum creatinine. Neither group required increased doses of steroid to compensate for lack of cyclosporine. From these data we can recommend conversion from cyclosporine to azathioprine in patients with cytotoxic antibodies or those undergoing retransplantation.

Actuarial Analysis↗
PubMed1989

Mycotic thoracic aortic aneurysm producing vertebral body destruction and paraplegia: case report.

In the surgical treatment of an aortic aneurysm, disruption of the blood supply to the spinal cord, resulting in paraplegia and anaesthesia below the level of involvement, is a dreaded complication. Occasionally, when an aortic aneurysm compresses a major vessel that supplies the anterior spinal artery, spinal cord ischaemia and paraplegia can occur before surgery. In the case presented here, however, preoperative paraplegia appears to have resulted from direct spinal destruction by an infected aortic aneurysm that was originally diagnosed as a spinal abscess. The patient underwent operative repair, but her aorta was so friable that the sutures would not hold. Despite repeat surgery, her condition rapidly proved fatal. This case shows that, in patients with a suspected spinal abscess, computer tomographic scanning and angiography should be performed to confirm the diagnosis and to rule out other pathological conditions. An accurate pre-operative diagnosis will permit adequate operative planning and prevent catastrophic results.

Aortic Aneurysm↗
PubMed1988

Successful transplantation of blood group A2 kidneys into non-A recipients.

The ABO subgroup A2 has been reported to be less reactive with the anti-A1 antibody naturally occurring in the serum of group O and B recipients and to occur in approximately 20% of group A individuals. Between March 1986 and February 1987, the Midwest Organ Bank (MOB) in Kansas City, screened all group A renal donors for the A2 subgroup. A total of 190 cadaverdonor kidneys were retrieved during this time, of which 68 were subgroup A1 and 16 were subgroup A2 (incidence of A2 = 19% of As and 8.5% of all donors). Of the subgroup A2 kidneys, 13 were transplanted into 9 group O and 4 group B recipients. One group O recipient received an HLA-identical A2 living-related graft. Recipients were not preselected or modified by splenectomy, plasmapheresis, or other means, and were treated with cyclosporine, steroids--and, in most cases, azathioprine, after transplantation. There was one hyperacute rejection and there were 5 acute cellular rejection episodes, 3 of which were reversed. One additional patient died at 2.5 months with a functioning graft. Including the successful living-related graft, 10 of 14 patients (71%) have functioning grafts, with a follow-up of 5 to 14 months, and a mean creatinine of 1.7 mg/dl. We find that the A2 subgroup represents a small but important minority of A donors, and that transplantation into non-A recipients can generally, but not universally, be safely accomplished. We recommend the screening of A donors for the A2 subgroup in both the cadaver-donor and living-related groups, and suggest that the utilization of A2 donors in non-A patients may contribute to the transplantation of group O and highly sensitized patients--and, in some cases, improve the degree of HLA matching.

ABO Blood-Group System↗
PubMed1985

Anaphylactic reaction and cardiopulmonary arrest following intravenous cyclosporine.

Cyclosporine, a new immunosuppressive agent useful in recipients of a variety of organ transplants, has been associated with a number of adverse effects, most notably nephrotoxicity. This report describes a woman about to undergo liver transplantation in whom intravenous administration of cyclosporine was associated with an apparent anaphylactic reaction resulting in cardiopulmonary arrest. Similar reactions have thus far not been reported after oral administration of cyclosporine. Intravenous cyclosporine must be administered under close supervision and should be avoided in any patients with a history of prior allergic reactions to the drug or to a component of its intravenous formulation.

Adult↗
PubMed1984

The use of local allograft irradiation following renal transplantation.

Over a 10 year period, 67 recipients of 71 renal allografts received graft irradiation following the diagnosis of rejection. The majority of kidneys were treated with a total dose of 600 rad, 150 rad per fraction, in 4 daily fractions. Fifty-three kidneys were irradiated following the failure of standard systemic immunosuppression and maximally tolerated antirejection measures (pulse high dose steroids, Actinomycin, ATG) to reverse an episode of acute rejection. Seven of these patients (13%) had greater than a 50% improvement in serum creatinine (Cr) 1 week following completion of the irradiation. Twenty-two (42%) of these allografts were noted to have stable (i.e. no deterioration) or improved function 1 month following the treatment with irradiation. Eleven (21%) of these allografts maintained function 1 year following transplantation. There were 10 patients whose allografts were irradiated because of renal dysfunction in a clinical setting which did not permit the administration of further immunosuppression, i.e., infection or hematologic dyscrasias. Three of these patients (30%) had greater than a 50% improvement in serum Cr 1 week following completion of the irradiation. Nine (90%) of these allografts had stable or improved function 1 month following the treatment with irradiation. Biopsies were obtained of 41 allografts. Of the 24 renal allografts with predominantly cellular rejection, 10 (42%) had the process reversed or stabilized at 1 month following irradiation. Five (21%) of these allografts were functioning at 1 year following irradiation. Rejection was reversed or stabilized in 6 of 17 (35%) allografts at 1 month when the histologic features of renal biopsy suggested predominantly vascular rejection. One (6%) of these allografts was functioning at 1 year following transplantation. Local graft irradiation has helped maintain a limited number of allografts in patients whose rejection has failed to respond to systemic immunosuppression. Irradiation may also benefit patients with ongoing rejection in whom further systemic immunosuppression is contra-indicated.

Adult↗
PubMed1984

Evolving use of OKT3 monoclonal antibody for treatment of renal allograft rejection.

OKT3, a monoclonal antibody reactive with a surface glycoprotein present on all postthymic T cells, was used to treat the initial acute episode of rejection in 30 recipients of cadaveric donor renal allografts. The first 16 patients received 1-5 mg daily for a period of 10-21 days during which the azathioprine and prednisone dosages were sharply reduced. Circulating T cells were eliminated within minutes after the first OKT3 infusion. T cells reactive with OKT3 remained depressed throughout the period of treatment, although a significant number of cells reactive with other T cells subset reagents became detectable after several days of OKT3 treatment. In all instances, the established rejection episode was reversed in 2-8 days without the addition of other immunosuppressive measures. Recurrent rejection occurred in 12 of 16 patients, but with further conventional immunosuppression, 50% of the renal allografts remain functional 20-44 months after transplantation. Fever, chills, and, in some instances, dyspnea following the first dose of OKT3 were the only side-effects observed. Most patients developed antiidiotypic or antimouse immunoglobulin antibodies without apparent clinical sequelae. In the subsequent 14 patients, modifications in the protocol included a steroid bolus prior to the first OKT3 infusion, limitation of therapy to 10 days, resumption of maintenance levels of azathioprine and prednisone prior to discontinuing OKT3, and addition of 3 i.v. doses of cyclophosphamide at the termination of treatment. Respiratory symptoms after the first infusion of the reagent have been eliminated. Antibody responses to OKT3 have been reduced, occurring in 38% as compared with 73% of patients treated previously. Recurrent rejection episodes observed in 8 of 14 patients have been reversible in all but one case. Allograft survival is 86% at 6-17 months posttransplantation. In the entire series of 30 OKT3-treated patients, only 4 grafts (13%) have been lost because of recurrent episodes of rejection.

Antibodies, Monoclonal↗
PubMed1984

Cyclosporine.

Cyclosporine is more selective in its suppression of the immune system than previously available drugs. Although the exact mechanism of action is not yet known, it probably acts by interfering with lymphokine secretion. It primarily inhibits T-lymphocyte responses, although some B cell responses are also affected. Neutrophils and platelet formation are spared. Its efficacy in prolonging the survival of transplanted organs in experimental animals has been a stimulus to the study of graft-host interactions and to the growth of clinical transplantation. In clinical renal transplantations, many, but not all, centers have observed an improvement in graft survival. Nephrotoxicity is common--the average creatinine level of a stable patient on cyclosporine is typically a third again higher than in a patient on conventional therapy. Results of studies up to three years have not shown a further deterioration in renal function, but longer term data are unavailable. Because patients on cyclosporine often have less severe rejection and require lower dosages of corticosteroids, progress in cardiac and hepatic transplantation is being made. The role of blood level monitoring in the avoidance of nephrotoxicity and other side effects remains unsettled. Only further experience with measuring concentrations of the drug in the blood will reveal if it is useful. Numerous drug interactions are important, particularly with aminoglycosides and amphotericin.

Animals↗