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Biomedical subjects

B M Frey

Publications and source records attributed to B M Frey.

99 records · Page 6Linked to original sources
PubMed1981

Endogenous hydrocortisone, a possible factor contributing to the genesis of cushingoid habitus in patients on prednisone.

To establish if the cushingoid habitus in patients taking prednisone is associated with relatively high total or free prednisolone and low endogenous hydrocortisone concentrations in plasma, 15 stable renal transplant patients and 12 patients treated with prednisone for oral mucocutaneous vesiculo-erosive diseases were investigated. After the patients' usual prednisone doses, the areas under the plasma concentration time curve of total and free prednisolone were not different when the 14 patients without cushingoid appearance were compared to the 13 patients with cushingoid appearance. Patients with cushingoid habitus more frequently exhibited peak hydrocortisone levels within the normal range (6 of 14 vs. 1 of 13) and had higher areas under the plasma concentration time curve of hydrocortisone (median, range), i.e. 2672 ng/ml.min (0-21, 637 ng/ml.min) vs. 308 ng/ml.min (0-12, 495 ng/ml.min) compared to those without cushingoid appearance (P less than 0.05). These results indicate that pharmacokinetic differences of prednisone do not explain the presence or absence of cushingoid habitus and that there is an association between cushingoid habitus and endogenous hydrocortisone levels.

Adult↗
PubMed1980

Prediction of the histological type of glomerulonephritis. Multiple discriminant analysis of clinical and laboratory characteristics at time of diagnosis.

We performed a prospective study on 68 subjects with biopsy-proven clomerulonephritis using a discriminant analysis of 12 clinical and laboratory characteristics. Among these, the selectivity of proteinuria, the presence of hematuria and the plasma level of C3 proved to be the most useful. An equation based on these three variables discriminated without overlap between 17 patients with minimal change glomerulonephritis (MCGN) and 30 patients with either membranoproliferative or rapidly progressive glomerulonephritis. However, some overlap existed between MCGN and focal sclerosis or membranous glomerulonephritis. In addition, the formula seems to identify steroid-resistant patients with MCGN.

Adolescent↗
PubMed1980

Prednisolone clearance at steady state in dogs.

The purposes of this study were: 1) to determine in dogs under steady-state conditions whether prednisolone clearance increases with increasing dose as has been suggested from results obtained under nonsteady-state conditions in man and 2) to determine whether the prednisolone to prednisone conversion, apparently resulting from 11 beta-hydroxydehydrogenase, is saturable. Six dogs were given four different zero-order infusions of prednisolone resulting in steady-state levels from 23 to 5884 ng/ml.Prednisone, total and free prednisolone levels were assessed by high-pressure liquid chromatography and equilibrium dialysis. Total and unbound prednisolone clearances were calculated by dividing the infusion rate by the total or unbound prednisolone concentration at steady state. Both total and unbound prednisolone clearance exhibited a slight tendency to decrease (P < .05) with increasing prednisolone steady-state levels. The conversion of prednisolone to prednisone, defined by the prednisolone/prednisone ratio, exhibited saturable characteristics which, when data for all dogs was fitted to a Michaelis-Menten type equation (r2 = 0.938), gave a Km of 658 ng/ml, i.e., total prednisolone concentration at half-maximal saturation.

Animals↗
PubMed1979

Selectivity as a clue to diagnosis of postural proteinuria.

In 14 patients with fixed and reproducible postural proteinuria and 14 patients with histologically proven glomerulonephritis, the selectivity of proteinuria was measured separately in the day and night urine collections. The selectivity of proteinuria in the urine collected in recumbency was lower in patients with glomerulonephritis than in patients with postural proteinuria. All patients with postural proteinuria showed an increment of the selectivity from day to night of at least 13 degrees, whereas the maximum increment in patients with glomerulonephritis was 5 degrees. The changes in selectivity from day to night in patients with postural proteinuria and patients with glomerulonephritis were significantly different and seem to be a useful discriminatory test.

Adolescent↗
PubMed1979

Liquid-chromatographic measurement of endogenous and exogenous glucocorticoids in plasma.

The therapeutic response to and side effects of glucocorticoids will be better recognized and the recovery of the adrenals during the tapering of therapy with steroids better evaluated if endogenous and exogenous glucocorticoids are separately assessed. We describe a specific method for simultaneously measuring the concentrations of cortisone, cortisol, prednisone, and prednisolone in plasma by "high-pressure" liquid chromatography. The steroids, together with an internal standard, dexamethasone, are extracted from 1 mL of plasma with methylene chloride-ether, washed with acid and base, and separated isocratically on a normal-phase silica column with a mobile phase consisting of methylene chloride/tetrahydrofuran/methanol/glacial acetic acid (96.85/1/2.1/0.05 by vol) at a flow rate of 1.3 mL/min. The steroids are detected at 254 nm and quantitated by peak-height measurements; their retention times range from 6 to 20 min. The lower limits for routine detection of all four compounds is 10 microgram/L. The analytical recoveries are about 75%; the intra-day variability (CV) is 1 to 9%, and the inter-day variability 2 to 11%. Of 26 drugs and 20 steroids tested, only theophylline presents an interference problem.

Chromatography, High Pressure Liquid↗
PubMed1977

[Proteinuria and kidney transplantation. A quantitative immunochemical study of 7 protein clearances during the first 50 days following implantation of cadaver kidney].

During the initial 50 days following transplantation of a cadaver kidney into 8 patients, determinations of 7 individual protein clearances were performed twice a week. This, the first posttransplantation investigation of single protein clearances utilizing unconcentrated urine, was made possible by the highly sensitive electroimmunodiffusion method of LAURELL [24]. The following results were obtained: 1. Kidney implantation was immediately followed by glomerulo-tubular proteinuria. In patients exhibiting good transplant tolerance the tubular proteins disappeared from the urine by the 43rd day at the latest; on the other hand, excretion of the glomerular proteins transferrin and albumin continued. In patients without complications the proteinuria was already highly selective by the 7th day (70 degrees). 2. In 5 of 8 patients there was a change in the proteinuria pattern during the rejection crisis: glomerulo-tubular proteinuria occurred three times and glomerular proteinuria twice. In two of these cases there was a change in the selectivity. 3. Patients with good tolerance showed plasma prealbumin levels which increased as a function of the time lapse since transplantation. 4. The plasma concentration of retinol-binding protein did not vary following transplantation and remained at 16.8 +/- 2.8 mg% in patients with uneventful course and at 18.5 +/- 4.9 mg% in patients with transplant rejection reactions, both values being markedly above the norm (4.7 +/- 1.1 mg%, [1 SD]).

Adult↗
PubMedDate not supplied

Marked interspecies differences between humans and pigs in cyclosporine and prednisolone disposition.

Pigs have been used extensively in various transplantation protocols. Immunosuppressive therapy is usually performed by steroids and cyclosporine A (CyA). For rational dosage of these xenobiotics, their pharmacokinetics should be characterized. Therefore, we investigated the kinetics of prednisolone, an immunobiologically active steroid, after oral and iv administration, and of CyA, after oral and iv dosing, in seven pigs and compared these results with those obtained in 20 renal transplant patients. The mean area under the blood concentration versus time curve of CyA (HPLC measurements) was lower in pigs than in humans after oral (67 +/- 31 micrograms/ml x min vs. 296 +/- 101 micrograms/ml x min) and after iv (358 +/- 71 micrograms/ml x min vs. 858 +/- 292 micrograms/ml x min) doses of CyA. Compared to humans, pigs had lower concentrations of total prednisolone--assessed by HPLC--after oral prednisone (7.1 +/- 4.3 micrograms/ml x min vs. 297.9 +/- 75.6 micrograms/ml x min) and after iv prednisolone (26.8 +/- 9.5 micrograms/ml x min vs. 373.3 +/- 77.7 micrograms/ml x min). The plasma concentrations of both agents, lower in pigs than in humans, were attributable to an increased volume of distribution, an increased clearance, and more of a diminished systemic availability in pigs than in humans. Thus, to obtain the same target concentrations of CyA and prednisolone in both species, pigs require about 2 to 4 times higher iv or oral doses of CyA and 10 to 30 times higher iv or oral doses of steroids.

Administration, Oral↗