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Biomedical subjects

M E Brunson

Publications and source records attributed to M E Brunson.

30 records · Page 2Linked to original sources
PubMed1992

Immunosuppression without prophylactic antilymphocyte preparations.

1. Triple-drug immunosuppression following third party transfusion can result in graft survival equal to protocols that employ prophylactic antilymphocyte preparations. 2. T1/2 was statistically improved in cadaveric and living-related donor grafts in the CsA era. 3. Patients 65 years and older had an excessive death rate. Younger groups were admixed. Extreme youth was not a risk factor. 4. Black recipients had excessive late graft loss. 5. Diabetic recipients had only a slight decline in graft and patient survival rates. 6. First and multiple graft recipients had similar transplant survival rates. 7. Delayed graft function remains costly in this immunosuppressive scheme.

Academic Medical Centers↗
PubMed1991

Depletion of dietary arginine inhibits growth of metastatic tumor.

The effects of dietary arginine on the growth of a murine colon tumor metastatic to the liver were examined in a model of advanced neoplastic disease. Tumor growth was influenced by arginine both in vivo and in vitro. An arginine-supplemented diet stimulated tumor growth by 55% compared with controls. Conversely, an arginine-depleted diet inhibited tumor growth by 78% compared with controls. In vitro culture of both murine and human colon tumor cells confirmed that arginine was necessary for cell growth. Flow-cytometric analysis using propidium iodide and bromodeoxyuridine suggested that colon tumor cells cultured without arginine enter a quiescent S phase and depend on arginine for further growth and cell cycle progression. The potential roles for selective dietary arginine modulation in patients with cancer with advanced disease are discussed.

Adenocarcinoma↗
PubMed1991

Selection criteria for liver transplant donors.

As the number of successful liver transplants has increased, the demand for donors has outpaced the supply. Approximately 25% of patients die awaiting an appropriate donor. Current criteria for assessing potential donors need to be closely examined. Fifty-six potential donors were evaluated by our transplant team by utilizing standard liver function tests (LFT's)-SGOT, SGPT, bilirubin. Additionally, a lidocaine metabolism test was performed by giving a 1 mg/kg IV dose of lidocaine over 1 minute and measuring the accumulation of the major metabolite monoethylglycinxylidide (MEGX) at 15 minutes by fluorescent polarization immunoassay (Abbott Diagnostics, Abbott Park, IL). Previous work has suggested that a MEGX less than 50 ng/mL is associated with initial non-function. Thirty-four donors were transplanted (group I) and all had initial function (all MEGX values were greater than 50). Twenty-two donors (39%) were judged unacceptable (group II) by our transplant team and by outside centers based upon one of the following criteria: II A) elevated LFT's--8, 11 B) donor age--5, II C) donor instability--4, II D) no available recipient--3, II E) miscellaneous--2. Standard LFT's were not statistically different in the donors used and in those not used when excluding category II A. Six of seven donors excluded in group I had acceptable MEGX values indicating they may have been transplantable. Ten of 12 patients excluded in groups II B-D had normal LFT's and nine of 12 had acceptable MEGX values indicating they may have been transplantable also. In this era of organ shortage, a reevaluation of donor selection criteria utilizing new tests like MEGX may be necessary to meet the increased need.

Adolescent↗
PubMed1991

Enhancement of allograft survival by donor-specific transfusion one day prior to transplant. Importance of timing and specificity when DST is given with cyclosporine.

Donor-specific transfusion effects were studied in the ACI-to-Lewis rat heterotopic heart allograft model using cyclosporine immunosuppression. Low-dose CsA for 1 week plus a single fresh or stored DST given 1 day before allografting significantly prolonged graft survival over CsA therapy alone (median survival time 23.5 days vs. 10 days, P less than 0.01), but third-party transfusion did not (11.5 vs. 10 days, NS). When CsA was started at the time of DST and continued for 2 weeks, maximal graft enhancement was achieved after just one DST. DST/CsA was equally efficacious if given on any day before transplantation, provided CsA was started on the same day as the transfusion. However, pretransplant DST given without CsA shortened subsequent graft survival of day -1 DST/CsA treatment (14.5 days, n = 6, vs. 60 days for controls, n = 10; P less than 0.01). The addition of methylprednisolone to the DST/CsA protocol had no effect on graft survival (51 vs. 53 days, P = NS), but extending the period of postoperative CsA therapy for 4 weeks at reduced dose (2.5 mg/kg/day) significantly prolonged median survival (111 days, n = 11) and resulted in 45% permanent engraftment (greater than 120 days survival). CsA permits graft enhancement with a single DST as early as 1 day before grafting. This avoids the risk of sensitization from DSTs and can extend DST use to cadaveric graft recipients.

Animals↗
PubMed1990

Variable infection risk following allogeneic blood transfusions.

These studies address infection risk of allogeneic transfusion in an untraumatized, nonseptic rodent model. A' Segaloff Cancer Institute rats served as blood donors and Lewis rats as recipients. Lewis rats' delayed-type hypersensitivity (DTH) response and their ability to clear subdermal Staphylococcus aureus abscesses and Candida albicans pyelonephritis were measured as tests of the effect of transfusions. The effect of pharmacological immunosuppression with either cortisone acetate or cyclosporine provided a "yardstick" to measure the magnitude of transfusion effects. Repeated transfusions at 1-week intervals diminished DTH response to recall antigens (keyhole limpet hemocyanin), but otherwise they showed no evidence of immunosuppression in these experiments. In contrast, we found that transfusions by themselves produced mild immunostimulation. Subcutaneous Staphylococcus abscesses were smaller in animals receiving transfusions. The magnitude of immunostimulation from one transfusion was sufficient to reverse the immunosuppressive effect of cyclosporine by about 50% in a Candida pyelonephritis infection. These studies suggest that blood transfusions have complex interactions with different components of the immune response. T-cell function is impaired by repeated transfusions (diminished DTH response), but other inflammatory responses are accentuated. This suggests that blood transfusions may harm immune response in traumatized animals by causing excessive complement activation or cytokine release.

Abscess↗
PubMed1990

HLA and Kaposi's sarcoma in solid organ transplantation.

Of 188 cases of Kaposi's sarcoma arising de novo after transplantation, HLA-A, -B typing was available for 135 and HLA-DR typing available for 67. Compared to the reported HLA phenotype frequencies of renal transplant recipients in the Southeast Organ Procurement Foundation (SEOPF), there is a significantly decreased frequency of HLA-A1 and HLA-B7, and increased frequency of HLA-B5, -B8, -B18, and -DR5. The most striking characteristic of the Kaposi's sarcoma group was its ethnic background. Fifty-six percent of patients were Italian, Greek, Jewish, or Arabic. When this ethnic background is considered, the expected HLA phenotype frequencies are almost exactly the same as in the Kaposi's sarcoma population. The quality of donor-recipient HLA match was evaluable for 106 patients. Only 22% had four or more mismatches, and 59% had at least two antigens matched. This argues against poor donor-recipient matching as a risk factor for developing Kaposi's sarcoma after transplantation.

HLA Antigens↗
PubMed1989

A comparison of the clinical utility of the radioimmunoassay, high-performance liquid chromatography, and TDx cyclosporine assays in outpatient renal transplant recipients.

Rapid and precise cyclosporine measurements are necessary to maximize immunosuppression and minimize toxicity. The new cyclosporine and metabolites TDx fluorescent polarization immunoassay was studied to determine its precision, sensitivity, and stability. Further, it was compared with the existing radioimmunoassay and high-performance liquid chromatography assays for clinical utility. The TDx procedure utilizes 50 microliter of serum or blood. The range of the assay is 0-1000 ng/ml for serum and 0-2000 ng/ml for whole blood. Precision studies of three control levels provided coefficients of variation of 2.1-5.8% for both assays. The sensitivities of the assays were less than 25 ng/ml for serum and less than 50 ng/ml for whole blood. In order to compare the TDx with the currently used RIA and HPLC methods, 362 simultaneous whole blood and serum samples were obtained from 122 renal transplant recipients over a 4-month period. The serum and whole blood TDx assays excluded fewer patients than either the RIA or HPLC assays with regard to sensitivity. The mean serum cyclosporine concentration for samples above the sensitivity was as follows: TDx 120 +/- 5 ng/ml, RIA 116 +/- 4 ng/ml, and HPLC 100 +/- 5 ng/ml. The mean whole-blood cyclosporine concentration for samples above the sensitivity was as follows: TDx 585 +/- 19 ng/ml, RIA 543 +/- 14 ng/ml, and HPLC 178 +/- 5 ng/ml. Serum and blood TDx levels correlated well with RIA levels, with regression coefficients of r = 0.813 and r = 0.897, respectively. Serum and blood TDx levels did not correlate strongly with HPLC levels, with regression coefficients of 0.332 and 0.781, respectively. Seventeen patients were diagnosed as having acute cyclosporine nephrotoxicity. The serum and whole-blood cyclosporine concentrations in these patients were at the upper end of the therapeutic range for all analytical methods. Five patients had acute cellular rejection; serum and whole-blood cyclosporine levels in these patients did not differ significantly from the stable patients when measured by each of the analytical methods. In conclusion, the TDx cyclosporine and metabolites assay provides reliable blood and serum concentrations that correlate well with RIA measurements in renal transplant recipients. This assay offers rapid sample turn-around times making possible same-day results for all patients without putting great demands upon the laboratory.

Ambulatory Care↗
PubMed1988

Effect of various prokinetic agents on post Roux-en-Y gastric emptying. Experimental and clinical observations.

The effect of various prokinetic drugs was assessed in animals with Roux-en-Y gastrojejunostomy. The agents tested were (1) bethanechol 2.5 mg subcutaneously at 0 min and 30 min postprandially (pp); (2) metoclopramide 20 mg intravenous bolus at 0 min pp; (3) a combination of 1 and 2; (4) oxytocin 5 mg intramuscularly at 0 min and 240 min pp; (5) motilin at 100 ng/kg/hr; or (6) 300 ng/kg/hr continuous intravenous infusion from 0 to 270 min pp. Only bethanechol administration resulted in significantly less gastric retention (65 +/- 6% vs 32 +/- 5% retention at 5 hr). (P less than 0.002). The animal results with parenteral bethanechol were confirmed in humans with chronic delayed gastric emptying following Roux-en-Y gastrojejunostomy, with a decrease in gastric retention on radionuclide scan from 78.5 +/- 5% to 26 +/- 12% at 2 hr pp (P less than 0.01). Initially all patients responded with symptomatic improvement. However, subsequently 3/6 (50%) of patients required total or near total gastrectomy for recurrent symptoms of gastric stasis. Nevertheless, 2/6 (33%) of patients have no further evidence of gastric stasis, and a trial of bethanechol is recommended prior to considering further gastrectomy in patients with the Roux-stasis syndrome.

Animals↗