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Biomedical subjects

M Floyd

Publications and source records attributed to M Floyd.

At least 55 records · Page 3Linked to original sources
PubMed1980

Prednisolone clearance in renal transplantation.

Although prednisolone is the most common immunosuppressive agent used in renal transplantation, an accurate formulation of the optimal dose regimen remains to be established. A sensitive and precise radioimmunoassay was developed for this purpose. Fifty microliters of 1:20 dilutions of serum or 1:200 dilutions of urine were incubated at room temperature for two hours with 130 pg of 3H-prednisolone (150muCi/microgram) and a rabbit antiserum against prednisolone (1:1,600 dilution). Serial prednisolone clearances (Cp) for ten renal transplant patients representing variable allograft functions were compared with their corresponding creatine clearances (Cer). The data show that renal metabolism of prednisolone is well correlated with Ccr. Increasing (decreasing) Ccr is accompanied by increasing (decreasing) Cp. The availability of an assay for serum prednisolone, together with a knowledge of the ratio between these two clearances, may prove useful for regulating therapy in renal transplant patients.

Dose-Response Relationship, Drug↗
PubMed1980

Quantitation of plasma azathioprine and 6-mercaptopurine levels in renal transplant patients.

The plasma of renal transplant patients was analyzed by high performance liquid chromatography (HPLC) for the presence of azathioprine and its primary metabolite, 6-mercaptopurine, after either oral or i.v. administration of azathioprine. Azathioprine was demonstrated in plasma at peak concentrations of 0.6 microgram/ml 15 min after i.v. injections of 100 to 200 mg. Within 90 min of injection, the azathioprine level fell to 10 ng/ml. Azathioprine was not detected in plasma at any time after an oral dose of 100 mg, indicating that the plasma concentration is less than 0.5 ng/ml, which is the sensitivity limit of this assay. 6-Mercaptopurine appeared in the plasma after either oral or i.v. azathioprine administration. Furthermore, decreased renal graft function has no effect on the rate of disappearance of azathioprine from plasma. These results demonstrate that high performance liquid chromatography can be used to determine azathioprine and 6-mercaptopurine levels in man, and that alteration in renal function does not influence early stages of azathioprine degradation.

Administration, Oral↗
PubMed1980

Improved allograft survival of strong immune responder-high risk recipients with adjuvant antithymocyte globulin therapy.

The pretransplant cellular immune responsiveness of 90 renal failure patients was correlated with subsequent allograft survival. Patients were subdivided in two bases: whether the pretransplant immune parameter values were above (strong responder) or below (weak responder) the group median, and whether they were responsive or anergic to recall skin test antigens. In a group of 72 cadaveric renal allograft recipients, treated with only Imuran and prednisone, the overall 1-year graft survival was 48%. Pretransplant immunocompetence correlated with graft survival: factors predicting longer allograft survival (P < 0.01) included: percentage of active T rosette-forming cells (A-T RFCs) < 36.5%, anergy to microbial skin test (ST) antigens, in vitro spontaneous blastogenesis (SB) < 14,600 cpm, and response to a panel of five donors in mixed lymphocyte culture (PMLC) < 28,000 cpm. In the two groups, weak and strong responders, the 1-year graft survival rates differed: 63% versus 32% when segregated by the A-T RFC parameter, 63% versus 33% for ST, 57% versus 36% for SB, and 63% versus 35% for PMLC. There were no significant differences in the number of HLA mismatches between the two groups. An additional group of 18 patients was treated with adjuvant immunosuppressive therapy by prophylactic administration of antithymocyte globulin (ATG; Upjohn Co.). Strong, but not weak, responders treated with ATG displayed a significantly improved (P < 0.01) 1-year graft survival over that of the untreated group. Thus, pretransplant immunological assessment may guide the selection of adjuvant immunosuppressive therapy to improve renal allograft survival in strong immune responders at high risk of rejection.

Antilymphocyte Serum↗
PubMed1980

beta 2-Microglobulin clearance as measured by radioimmunoassay.

We describe a radioimmunoassay for beta 2-microglobulin (beta 2 mu) in serum and urine. We incubated aliquots of diluted samples at room temperature for 1 h with 125I-labeled beta 2 mu and a rabbit antiserum monospecific for human beta 2 mu, and separated the phases by the double-antibody technique. The logit-log transformed dose-response curve was linear in the range 2 to 64 ng, equivalent to 0.5 to 16 mg/L of serum and 0.5 to 320 mg/L of urine. Assay sensitivity was 2.4 ng of beta 2 mu. Validation studies included tests of precision, accuracy, antibody specificity, and parallelism of the dose-response curves for standard and unknown. In a study of 25 normal individuals, serum and urine beta 2 mu ranged from 1.1 to 2.3 mg/L and 40 to 360 micrograms/24 h; the clearance of beta 2 mu was 8 to 130 microL/min. In 21 renal allograft recipients tested one to five weeks after transplantation, serum and urine beta 2 mu ranged from 3.9 to 15.6 mg/L and 7.2 to 611 mg/24 h; beta 2 mu clearance was 0.60 to 33.3 mL/min. Values for both serum and urine correlated well with severity of allograft rejection.

Beta-Globulins↗
PubMed1980

Cutaneous lesions due to Mycobacterium kansasii.

A recipient of a renal homograft had cutaneous lesions on the lower extremities that resembled pyogenic abscesses. Staphylococcus aureus consistently grew from cultures and despite appropriate antibiotics, the lesions did not completely resolve. When special cultures were done, Mycobacterium kansasii was discovered. In immunocompromised patients with infectious cutaneous lesions, skin biopsy using appropriate stains and cultures should be considered early in the course of the illness.

Adult↗
PubMed1979

The role of IgM rheumatoid factor in experimental immune vasculitis.

The effect of IgM rhematoid factor (RF) on reversepassive cutaneous Arthus reaction in rats was studied. The RF was obtained from the serum cryoglobulin of a patient with symptoms of purpura, arthralgia and digital gangrene. The cryoglobulins was of IgG-IgM type and when given i.v it induced a prompt hypocomplementaemia in experimental animals. The purified RF also induced low serum complement levels when injected i.v. along with complexes of non-complement-fixing, aggregated IgG. A reverse passive Arthus reaction was induced by intradermal injection of IgG anti-bovine serum albumin (BSA), followed by an i.v. dose of antigen (Ag). The cutaneous inflammatory reaction was aggravated by simultaneous administration of IgM RF intradermally, but not by IgM without antibody (Ab) properties. Intradermal injection of low concentrations of non-complement-fixing IgG anti-BSA, along with normal human IgM, followed by i.v. injection of BSA, resulted in a complete lack of cutaneous inflammation. At higher Ab concentrations there was only a mild inflammation. However, when IgM RF was substituted for normal IgM and injected with non-complement-fixing anti-BSA, an effective reverse passive cutaneous Arthus reaction and vasculitis was induced. The inflammatory response was greatly suppressed by decomplementation of animals by cobra venom factor. This study provides evidence favouring an inflammatory, complement-dependent role for RF in vasculitis.

Animals↗
PubMed1979

Radioimmunoassay for immunologlobulin G in serum and urine.

We describe a radioimmunoassay for immunoglobulin G (IgG) in serum and urine. Aliquots of diluted samples and 125I-labeled IgG were incubated in antibody-coated tubes at 37 degrees C for 24 h, the supernates were decanted, and the radioactivity in tubes containing the bound fraction was counted. The dose-response curve in the range of 0.4--500 mg/L of urine or 640--40 000 mg/L of serum was linear on logit-log transformation and iterative weighted regression. Assay sensitivity was 10 ng of IgG. Validation studies included testing for precision, accuracy, antibody specificity, and parallelism of the dose-response curves for standard and unknown. In a study of 14 apparently normal individuals, serum IgG = 4.0-10.9 gL, urine IgG = 1.1-4.8 mg/24 h, and IgG clearance = 0.2 X 10(-4) to 4.8 X 10(-4) mL/min. In 20 patients with renal allografts, serum IgG = 15.8-66 g/L, urine IgG - 9.6-626 mg/24 h, and IgG clearance = 9 X 10(-4) to 1.99 X 10(-1) mL/min. IgG values correlated well with severity of renal allograft rejection.

Graft Rejection↗
PubMed1979

Demonstration by radionuclide imaging of possible vascular steal from a renal transplant.

Radionuclide studies in a renal-transplant patient with congestive heart failure suggested vascular steal from the renal allograft by a contralateral femoral arteriovenous fistula. These reliable, noninvasive diagnostic procedures have potential use in similar settings to evaluate allograft perfusion and function. Correction by removal of the fistula was demonstrated.

Adult↗
PubMed1978

Radioimmunoassay for urinary albumin.

We describe a rapid, sensitive, and precise radioimmunoassay for urinary albumin (Ualb). Aliquots of diluted urine were incubated at room temperature for 1 h with 125I-labeled albumin and a rabbit antiserum monospecific for human albumin. Phase separation was effected by the double-antibody technique. The dose-response curve as linear in the range of 15.6-10000 ng, equivalent to 4 to 3000 mg/liter of urine. The limit of sensitivity was 16 ng of albumin. The coefficient of assay variation was 4.8%, both at 44 mg/liter and at 1304 mg/liter. A displacement curve obtained with a serially diluted urine sample of high albumin concentration was completely superimposable with the curve for which human albumin was used as a standard. In 26 normal individuals the range for Ualb was 2.2--12.6 mg/24h, and for albumin clearance (Calb, 1.8 x 10(-5)-19.6 x 10(-5) ml/min. After renal homografts in 25 patients, Ualb ranged from 16.9 to 9928 mg/24 h, and Calb from 2.7 x 10(-4) to 1.7 x 10(-1) ml/min. Both increased Ualb and Calb correlated well with the severity of renal homograft rejection.

Albuminuria↗
PubMed1975

A nephropathy occuring in rats treated with dinitrochlorobenzene and N-methyl-N-nitroso guanidine.

Chronic administration of a potent oral carcinogen N-Methyl-N-Nitroso guanidine (M.N.N.G.) failed to produce gastric carcinoma in CFHB Wistar rats sensitised to 2.4 dinitrochlorobenzene (D.N.C.B.). In addition animals receiving both D.N.C.B. alone and D.N.C.B. and M.N.N.G. developed a severe nephropathy characterised by heavy proteinuria and extensive renal cortical damage. The histological features include proliferation of parietal epithelial cells and mesangial sclerosis. An association between the nephropathy and long term D.N.C.B. administration is suggested and on the basis of investigation to date direct toxicity rather than immune complex disease seems more likely.

Animals↗
PubMed1973

Fibrinogen catabolism study of three patients with bacterial endocarditis and renal disease.

Three patients with bacterial endocarditis who developed renal failure have been studied by means of a radiofibrinogen catabolism study. Two were studied at the time of bacteraemia and one during the subsequent "immunological phase" of circulating immune complexes. Accelerated fibrinogen catabolism was found in all cases. Intravascular coagulation may be an important factor in the pathogenesis of proliferative glomerulonephritis in such cases.

Acute Kidney Injury↗