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Biomedical subjects

F J Frey

Publications and source records attributed to F J Frey.

At least 127 records · Page 7Linked to original sources
PubMed1987

[Immunosuppressive therapy in clinical practice].

In clinical practice immunosuppressive therapy is performed by means of glucocorticoids in most patients. In addition, some patients are given alkylating agents (cytoxan, chlorambucil) or purine analogues (azathioprine). Recently a new immunosuppressive drug, cyclosporine A, has been developed. The mechanisms of action of these four compounds are discussed, for which purpose a simple model of the immunological network is presented. The present indications for the use of cyclosporine A in clinical practice are discussed.

Alkylating Agents↗
PubMed1987

[Immunoadsorption of anti-B antibodies as preparation for an ABO-incompatible kidney transplantation].

AB0-incompatible kidney transplantation involves major risk of early acute vascular rejection. We report for the first time the successful preparation for renal homografting of a recipient of an HLA-haplotype identical, AB0 blood group B-incompatible renal homograft from a living related donor by immunoadsorption for removal of B blood group antibodies at days -4, -2 and -1. The iso-agglutinin anti-B titer was 1:256 before and 1:8 after three adsorption sessions in extracorporeal circuit. Before and after transplantation the splenectomized recipient was given azathioprine, prednisone and cyclosporine A. After homografting the anti-B iso-agglutinin and the anti-B isoimmune titers were mostly below 1:8 and never exceeded 1:32 and 1:64 respectively. 111 days after transplantation the recipient had a creatinine concentration in plasma of 160-180 mumol/l and was free of infectious complications. Thus the introduction of specific and convenient immunoadsorption of blood group antibodies by pheresis for preparation of renal homograft recipients may in future extend the indications for kidney transplantation in AB0-incompatible subjects, who have so far been denied the benefit of a living renal homograft.

ABO Blood-Group System↗
PubMed1987

Differential efficacy of mebendazole and albendazole against Necator americanus but not for Trichuris trichiura infestations.

The effect of single oral doses of albendazole 600 mg and mebendazole 1 g given to 56 and 60 men, respectively, with T. trichiura and/or N. americanus infestation has been studied. Both albendazole and mebendazole cured more than 90% of T. trichiura infestations, but only albendazole (95%) and not mebendazole (21%) had a high cure rate for N. americanus infestations. Thus, albendazole is the preferred benzimidazole derivate for the mass treatment of subjects with T. trichiura and/or N. americanus infestations.

Albendazole↗
PubMed1987

Evidence that cyclosporine does not affect the metabolism of prednisolone after renal transplantation.

The following investigation was performed to establish whether renal transplant patients treated with cyclosporine and prednisone have a decreased prednisolone catabolism and/or an increased systemic availability of oral prednisone when compared with patients treated with azathioprine and prednisone. Therefore we assessed, by HPLC and equilibrium dialysis, the total concentrations of prednisolone and prednisone and the unbound concentrations of prednisolone in plasma samples collected over 24 hr, and the 24-hr urinary excretion of prednisolone, prednisone, and 6 beta-hydroxyprednisolone after an i.v. dose of prednisolone and an equal oral dose of prednisone in 25 renal transplant patients on cyclosporine and in 25 patients on azathioprine and prednisone one month after transplantation. The metabolic clearance, the renal clearance, the volume of distribution, and the systemic availability of total and unbound prednisolone were identical in patients with and without cyclosporine. The apparent activities of the oxidoreductases involved in the biotransformation of prednisone into prednisolone and vice-versa were not affected by cyclosporine therapy. The fractional urinary excretions of 6 beta-hydroxyprednisolone increased with increasing metabolic clearance rate of prednisolone (r = 0.50, P less than 0.001). This relationship was not modulated by cyclosporine, indicating that cyclosporine does not affect the activity of the microsomal P-450-dependent 6 beta-hydroxylase. Thus, early after transplantation, patients on cyclosporine have a normal metabolism of prednisolone.

Azathioprine↗
PubMed1987

Distinct distribution of periarticular erosions of the bones of the hand in chronic renal failure.

The frequency of radiological changes of the bones of the hand in 142 patients on hemodialysis, 19 on CAPD, and 15 patients with advanced renal insufficiency not requiring dialysis was analyzed. Forty-seven percent of all patients had subperiostal cortical bone resorptions, 31% periarthritis calcarea, 22% periarticular erosions, 3% chondrocalcinosis and 1% aseptic necrosis. Sixty-six percent of the periarticular erosions were observed in the distal and proximal interphalangeal joints of fingers II, III, IV and V, whereas only 33% were found in the remaining joints (120 vs. 62, p less than 0.001). The distal interphalangeal joints showed about 70% more often periarticular erosions than the proximal interphalangeal joints (77 vs. 43, p less than 0.001). Since patients with chronic renal failure exhibit a decreasing incidence of periarticular erosions from the distal interphalangeal joints to the intercarpal joints, while patients with rheumatoid arthritis have their erosions preferentially localized in the proximal interphalangeal, metacarpophalangeal and wrist joints, it can be concluded that renal osteodystrophy causes a distinct distribution of periarticular erosions of the bones of the hand.

Arthritis↗
PubMed1987

Impact of physical training on the ultrastructure of midthigh muscle in normal subjects and in patients treated with glucocorticoids.

Exercise-training might be a logical method to reverse muscle atrophy and weakness in patients treated with glucocorticoids. The purpose of the present investigation was to establish whether a treatment with low dose prednisone (10 +/- 2.9 mg/d) modulates the effect of a moderate strength type isokinetic training during 7 wk (21 sessions of 20 min) on "muscle efficiency" (power output/muscle mass) and on concomitant changes in ultrastructure of the thigh muscle measured by quantitative electron-microscopic morphometry. Training caused a similar increase in "muscle efficiency" in patients on prednisone (n = 9) as in normal volunteers (n = 9). In normal subjects the increase in muscle efficiency was associated with an increase in sarcoplasm, whereas in patients on prednisone the functional improvement was associated with an increase in sarcoplasm, capillaries, and mitochondria content. Thus, a therapy with low dose prednisone does not abrogate training-induced improvement of muscle efficiency but modulates the ultrastructural response of the muscle to the training.

Exercise Therapy↗
PubMed1986

Pharmacokinetics of tenoxicam in patients with impaired renal function.

The pharmacokinetics of tenoxicam after a single oral dose of 20 mg has been studied in 12 patients with various degrees of decreased renal function. Unchanged tenoxicam and its 5'OH-metabolite in plasma and urine were determined by HPLC. The mean areas under the plasma concentration-time curve (138 +/- 53 micrograms/ml X h) and terminal half-lives in patients with impaired renal function did not differ from values previously reported in normal volunteers, nor did the peak concentration of tenoxicam. The half-life of 5'OH-tenoxicam and unchanged tenoxicam where the same. The urinary excretion of 5'OH-tenoxicam fell with decreasing renal function. Thus no dosage adjustment should be necessary and the usual daily dose of tenoxicam may be administered once daily also to patients with renal failure.

Adult↗
PubMed1986

Effect of liver function on the metabolism of prednisone and prednisolone in humans.

The systemic availability of total prednisone and unbound prednisolone, and the urinary excretion of 6 beta-hydroxyprednisolone, were measured after an oral dose of prednisone and an i.v. dose of prednisolone in 22 patients covering a wide range of liver function (galactose elimination capacity ranging from 3.3 mg/min X kg body wt to 9.2 mg/min X kg body wt). The area under the plasma concentration versus time curves of prednisolone and of prednisone decreased with increasing galactose elimination capacity. This dependency of the steroid concentrations on liver function was attributed to a decreased metabolic clearance and not to an increased systemic availability of the steroid given p.o. in patients with impaired liver function. The fractional excretion and the fractional clearance of 6 beta-hydroxyprednisolone declined with decreasing metabolic clearance rate of prednisolone or with decreasing galactose elimination capacity. Thus, the enzymes involved in the 6 beta-hydroxylation are not spared as liver function declines, and the exposure to the biologically active unbound prednisolone is increased in patients with impaired liver function in relation to the amount of prednisone or prednisolone administered.

Adult↗
PubMed1986

Altered skeletal muscle ultrastructure in renal transplant patients on prednisone.

Treatment with glucocorticoids causes wasting of proximal skeletal muscles. The purpose of the present investigation was to quantify in the thigh muscle the areas of the different fiber types determined by histochemical methods, and the muscle ultrastructure by means of electron microscopy, in normal subjects (N = 41) and in renal transplant patients treated with prednisone (N = 12). The cross-sectional area of all three fiber types was reduced in renal transplant patients treated with prednisone (10.6 +/- 4.3 mg/day), the fast glycolytic fibers being most affected (slow oxidative fibers: 2642 +/- 625 vs. 3677 +/- 970 micron2, P less than 0.001; fast oxidative fibers: 3275 +/- 735 vs. 4443 +/- 1343 micron2, P less than 0.01; fast glycolytic fibers: 2305 +/- 802 vs. 3920 +/- 1522 micron2, P less than 0.001). This was mostly due to a decrease in the volume of myofibrils per unit volume of muscle fiber (-30%). The intracellular lipid content and the volume density of subsarcolemmal mitochondria were increased by more than 70% in prednisone treated patients. In conclusion, the decreased myofibril areas might account for the muscle weakness in renal transplant patients treated with prednisone, and the decrease in myofibrils is in part functionally compensated by an increase in subsarcolemmal mitochondria and intracellular lipid content.

Adult↗
PubMed1986

Altered body fat distribution in patients with glucocorticoid treatment and in patients on long-term dialysis.

Fat distribution was assessed by computed tomography in normal volunteers (n = 42), patients on long-term dialysis (n = 18), and patients on glucocorticoids [renal transplant patients (n = 49), other diseases (n = 17)]. Patients on glucocorticoids had higher mediastinal (deep) and identical or increased posterior cervical, buccal, and midthigh (superficial) fat areas when compared with normal subjects. The pattern of fat distribution in dialysis patients mimicked the distribution observed in patients taking glucocorticoids. Healthy females had higher ratios of superficial to deep fat than healthy male subjects. Patients on prednisone or on dialysis lost this sex-associated difference in fat distribution. Since patients on prednisone exhibit increased or normal thigh fat depots in the presence of increased mediastinal fat, the current concept that glucocorticoids induce redistribution of body fat from peripheral to central fat compartments has to be revised. Furthermore, disease states and/or glucocorticoids abrogate sex-associated differences in body fat distribution.

Adipose Tissue↗
PubMed1986

The dose-dependent systemic availability of prednisone: one reason for the reduced biological effect of alternate-day prednisone.

An analysis of the literature was performed, revealing that in many studies both the desired and the undesired effects are decreased in alternate-day prednisone regimens as compared with the daily regimens. In the present report evidence is given that part of the diminished biological effect of dose-spacing regimens is attributable to a decreased total exposure to prednisolone. Following a high dose of 0.8 mg kg-1 of oral prednisone or prednisolone the plasma concentration vs time curves of total prednisolone, unbound prednisolone and prednisolone bound to albumin or transcortin were always less than four times higher than following a low dose of 0.2 mg kg-1 of prednisone or prednisolone. This dose-dependent systemic availability of prednisolone explains partly the diminished biological effect when the same total amount of prednisone or prednisolone is divided into several small doses as opposed to a single oral dose.

Administration, Oral↗
PubMed1986

Pharmacokinetics of carumonam in patients with renal insufficiency.

The pharmacokinetics of carumonam after a single 1,000-mg intravenous infusion (20 min) were evaluated in four groups of subjects who had various degrees of renal impairment: group 1, CLCR greater than 60 ml/min; group 2, CLCR = 30 to 60 ml/min; group 3, CLCR = 10 to 30 ml/min; and group 4, CLCR less than 10 ml/min). The elimination half-life of carumonam increased with decreasing creatinine clearance (CLCR) from 1.7 h in group 1 to 11.3 h in group 4. Peak carumonam concentration (103 micrograms/ml) and steady-state volume of distribution (12.8 liters) did not change with decreasing CLCR. Total body clearance (r = 0.98), renal clearance (r = 0.98), and nonrenal clearance (r = 0.67) of carumonam correlated with decreasing CLCR. Mean nonrenal clearance was 21 ml/min in group 1 and 12 ml/min in group 4. With regard to dosage, patients with a CLCR above 60 ml/min should receive their standard maintenance dose of carumonam without any changes; patients with a CLCR between 30 and 60 ml/min should receive the dose every 12 h; and individuals with a CLCR between 10 and 30 ml/min should be given the dose once a day. Patients with a CLCR of less than 10 ml/min should receive one-half of the dose once a day. Our recommended dosage regimens should produce within the CLCR borderlines of each group average plasma concentrations that are between one and two times that achieved in normal subjects with a t.i.d. dosage regimen.

Adult↗
PubMed1986

Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin.

Amoxicillin and clavulanic acid are prescribed as a fixed drug combination. The purpose of the present study was to assess the influence of various degrees of renal insufficiency (glomerular filtration rate [GFR], less than 5 to greater than 75 ml/min per 1.73 m2) on the pharmacokinetics of amoxicillin and clavulanic acid following oral (500 and 125 mg of amoxicillin and clavulanic acid, respectively) and intravenous (1,000 and 200 mg, respectively) dosing. The volume of distribution and the systemic availability were independent of the renal function, while the total body clearance and the renal and the nonrenal clearance of amoxicillin and clavulanic acid decreased with decreasing renal function. The decrease in the total body clearance was more pronounced for amoxicillin than for clavulanic acid. This explains the increase in the ratio of the area under the plasma concentration versus time curve of amoxicillin to that of clavulanic acid with decreasing glomerular filtration rate after oral dosing; for example for a GFR of 75 ml/min, the ratio of amoxicillin to clavulanic acid was 4.9 +/- 1.2; for a GFR of 35 to 75 ml/min, 5.3 +/- 2.4; for a GFR of 10 to 35 ml/min, 11.9 +/- 5.8; for a GFR of 5 to 10 ml/min, 13.4 +/- 9.1; and for patients on hemodialysis, 14.7 +/- 5.3. Dosage recommendations are suggested which prevent undue accumulations of amoxicillin while maintaining adequate concentrations of clavulanic acid.

Amoxicillin↗
PubMed1986

Renal artery embolism treated with intra-arterial streptokinase infusion results in patent but small renal arteries.

A low intra-arterial dose of streptokinase was used to dissolve a renal artery embolus in 2 patients. Angiography at the end of the streptokinase therapy disclosed patent renal arteries. Arteriograms performed 3 months and 2 years later demonstrated patent but small renal arteries. These cases confirm the limited experience reported in the literature that even though initial restoration of renal artery patency is possible, the ultimate renal function is poor after intra-arterial streptokinase therapy.

Adult↗
PubMed1985

[Medical problems in refugees from Sri Lanka (Tamil)].

Recently many refugees from Sri Lanka have arrived in Europe. The purpose of the present investigation was to analyze the subjective complaints and diagnoses in these refugees. One hundred refugees (97 males, 3 females, age 19 to 42 years) were investigated. The most common reasons for consulting a general internist were cough (23%), general pain in soft tissue and joints (21%), disorders of the gastrointestinal tract (19%) and ear or throat complaints (15%). In 43% of the patients no diagnosis could be established. 58 patients were investigated for parasites in stool: 57% of these patients had hookworms, 12% non-pathogenic protozoon, 9% Entamoeba histolytica cysts, and 2% Giardia lamblia. In 12% of the patients the diagnosis was tonsillitis or pharyngitis, in 7% bronchitis, pneumonia or asthma and in 5% arterial hypertension. Various other diagnoses were established in 48 patients. With the exception of the high frequency of intestinal parasites, complaints and diagnoses in these refugees were the same as in a comparable European population.

Adult↗
PubMed1985

Overestimation of renal function in glucocorticosteroid treated patients.

Creatinine clearance is commonly used as a parameter for individualization of dosages of drugs primarily excreted by the kidney. Nomograms and equations have been developed for estimating creatinine clearance from serum creatinine concentration, body weight, age and sex. Glucocorticosteroids are said to cause proximal muscle wasting and therefore may be expected to cause a decrease in the creatinine production rate. The purposes of the present investigation were first to evaluate by a computed tomography the effect of long term treatment with prednisone on the mid-thigh muscle area, and second, to establish whether the presumed supposed decrease in muscle mass was associated with a decrease in the urinary creatinine excretion rate, and hence in a systematic error whenever a nomogram is used to predict creatinine clearance in such subjects. Patients taking prednisone had smaller mid-thigh muscle areas than controls. A linear relationship between the mid-thigh muscle area and the observed urinary excretion of creatinine was found, suggesting that the muscle loss could account for the decrease in the urinary excretion rate of creatinine. The ratio of observed to predicted (by nomogram) urinary creatinine excretion was lower in patients than controls, resulting in a corresponding underprediction of creatinine clearance by nomograms in the patients taking prednisone.

Adult↗