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Biomedical subjects

H Flachs

Publications and source records attributed to H Flachs.

At least 37 records · Page 2Linked to original sources
PubMed1987

Glucocorticoid levels and lymphocyte functions in kidney transplanted patients.

The in vitro lymphocyte response to mitogen stimulation and the in vitro lymphocyte sensitivity to glucocorticoid were examined in 72 kidney transplanted patients before and after administration of high or low doses of glucocorticoid. Administration of 10 mg of prednisone orally to 10 patients did not significantly change the mitogen responses or the lymphocyte sensitivity to methylprednisolone. Likewise, administration of 100-120 mg of methylprednisolone, intravenously to 62 patients did not significantly affect the mitogen responses, but, in contrast, the lymphocyte sensitivity to the immunosuppressive effect of methylprednisolone was clearly increased. This effect was highly significant in both cyclosporine A and azathioprine treated patients. These findings suggest that a change of the lymphocyte sensitivity to the immunosuppressive effect of methylprednisolone may occur after a high dose of glucocorticoid, anaesthesia and surgery, although no changes of the immunefunctions in vitro can be demonstrated by examining the mitogen response of the lymphocyte cultures. No relationship was found in the present study between the individual lymphocyte sensitivity to glucocorticoid and metabolic clearance rate.

Adult↗
PubMed1987

Human pharmacokinetics of proguanil and its metabolites.

The pharmacokinetics of proguanil and its metabolites cycloguanil and p-chlorophenylbiguanide were studied in five healthy volunteers taking 200 mg orally for 14 days. A highly sensitive and specific high-performance liquid chromatographic assay was applied, clearly identifying all three compounds in plasma extracts as separate peaks. In four subjects peak plasma concentrations of proguanil (500 to 600 nmol/l) were reached after two to three hours, while cycloguanil and p-chlorophenylbiguanide showed a plateau after three and six hours, respectively. In the fifth subject peak concentrations of proguanil and cycloguanil appeared after seven hours. Trough concentrations (pre-dose in the morning) of proguanil and cycloguanil were about 200 and 100 nmol/l, respectively. Mean half-life of proguanil was estimated to approximately 20 h. The active metabolite cycloguanil constituted 30% of the total plasma drug concentration. The concentration of proguanil was higher in erythrocytes than in plasma, while that of cycloguanil was lower. Relevant clinical studies correlating plasma concentrations to the suppressive activity against malaria will be possible to perform based on the applied method and presented kinetic data.

Adult↗
PubMed1986

The effect of phenobarbital and carbamazepine on the ethanol withdrawal reaction in the rat.

The effects of phenobarbital (PB) and carbamazepine (CZ) on the ethanol withdrawal reaction in the rat were investigated in a blind study including an untreated control group. Physical ethanol dependence was established by intragastric intubation during a 4-day period. Both the degree of intoxication and the withdrawal reaction were assessed by standardised assessment instruments. Treatment with PB (40-60 mg/kg) and CZ (80-120 mg/kg) was initiated 10 h after the last ethanol dose and continued during the first 24 h of withdrawal. Serum concentrations of the drugs were measured. Both PB and CZ significantly reduced the ethanol withdrawal reaction compared to controls, and PB was significantly more effective than CZ. The degree of drug intoxication signs assessed by the same rating scale as the degree of ethanol intoxication indicated that maximum tolerable drug doses were used. PB probably exerts its treatment effect through the mechanism of cross dependence with ethanol, while CZ may exert a more specific effect on limbic structures responsible for central nervous system excitability.

Alcoholic Intoxication↗
PubMed1986

Effect of oral proguanil on human lymphocyte proliferation.

In vitro studies have indicated that the antifolates pyrimethamine [4, 6] and cycloguanil (the active metabolite of proguanil) suppress the proliferation of stimulated human lymphocytes; proguanil has no effect [2]. During the early growth phase of the cells, 14C-thymidine (14C-TdR) incorporation is increased by pyrimethamine and cycloguanil, reflecting blockage of endogenous TdR synthesis [3]. Proguanil (Paludrine) is increasingly being used for malaria prophylaxis. It is considered the most innocuous of the antimalarials currently employed. Since nothing is known about the effect of oral proguanil on human lymphocytes, the present study was undertaken. Little information is available about the serum levels of proguanil and cycloguanil following ingestion of prophylactic doses [8]. Therefore, the serum concentrations of proguanil and cycloguanil were estimated, to allow comparison with previous in vitro studies [2].

Adult↗
PubMed1986

Effect of chloroquine on human lymphocyte proliferation.

The effect of chloroquine on human blood mononuclear cells was studied. High concentrations of chloroquine in vitro profoundly suppressed the proliferation of mitogen- and antigen-stimulated cells, as indicated by decreased 14C-thymidine incorporation. Lower concentrations of chloroquine increased the response to pokeweed mitogen. The response to concanavalin A and to various antigens was suppressed, especially the response to large particulate antigens. Oral intake of 300 mg of chloroquine base/week did not affect the lymphocyte proliferative responses. 600 mg of base/week decreased the response to large particulate antigens; the response to small antigens was not affected. The mode of action of chloroquine and the possible consequences of the findings for dosage of chloroquine when used for malaria prophylaxis is discussed.

Antigens↗
PubMed1986

The susceptibility of Plasmodium falciparum to sulfadoxine and pyrimethamine: correlation of in vivo and in vitro results.

In 1982, 2 of 14 Plasmodium falciparum infections acquired in East Africa and diagnosed in Copenhagen were resistant to treatment with sulfadoxine plus pyrimethamine (Fansidar), while in 1983, 6 of 18 were so. The in vivo tests were supplemented by determinations of drug concentrations in serum, and 4 isolates from in vivo-sensitive cases and 6 from in vivo-resistant cases were selected for in vivo tests. These were performed in ordinary RPMI 1640 medium and in a medium with physiological p-aminobenzoic acid and folic acid concentrations. Pharmacokinetic aberrations were found to be of possible importance in only 2 of the in vivo-resistant cases. In vitro susceptibility to sulfadoxine was found to be uniformly low in all isolates. Testing with a combination of sulfadoxine and pyrimethamine in the medium with physiological concentrations of cofactors probably reflects the in vivo situation most accurately, but in all but 1 of the isolates studied in vitro the in vivo susceptibility to Fansidar would be predicted by in vitro susceptibility to pyrimethamine in either medium. The concentration of p-aminobenzoic acid in serum, quantitated by high performance liquid chromatography, was found to be subject to wide variation, and this may have implications for in vitro testing.

Adult↗
PubMed1986

In vitro effect of chloroquine, mefloquine and quinine on human lymphocyte proliferative responses to malaria antigens and other antigens/mitogens.

The effect of 3 antimalarial quinoline derivatives, chloroquine, mefloquine and quinine on human blood mononuclear cells in vitro was studied. High concentrations profoundly suppressed the proliferation of mitogen- and antigen-stimulated lymphocytes, as indicated by decreased 14C-thymidine incorporation. On a weight base, the most potent drug was mefloquine. At clinically relevant doses, chloroquine and mefloquine did not affect the response to malaria antigens, but mefloquine decreased the response to phytohaemagglutinin; quinine suppressed the response to all mitogens (with the exception of pokeweed mitogen) and antigens studied, including P. falciparum merozoites. The drugs' potential adverse effect on the immune system is discussed.

Adult↗
PubMed1986

Ketoconazole and cyclosporine A: combined effects on rat renal function and on serum and tissue cyclosporine A concentration.

The effects of ketoconazole (Kcnz) on cyclosporine A (CyA) serum levels and CyA-nephrotoxicity were studied. To rats later anesthetized with pentobarbital sodium, CyA 12.5 and Kcnz 20 mg/kg/day (n = 20), or CyA 12.5 mg/kg and Kcnz-vehicle (n = 21), was dosed. To rats anesthetized with etomidate (n = 14), CyA 12.5 mg/kg and Kcnz-carrier was dosed. S-CyA was monitored during 14 days, and then the rats were investigated with clearance (C) methods (inulin [(in), lithium (Li)], sodium, and potassium), and liver (L) and kidney (K) CyA was measured. Kcnz increased S-CyA, L-CyA and K-CyA (+50 -80%). There were significant (p less than 0.05) correlations between S- and L- or K-CyA. Kcnz increased CyA nephrotoxicity: Mean Cin was 1.012 ml/min/gKW (kidney weight) after CyA treatment (a subnormal value), but decreased to 0.556 ml/min/gKW in the group also given Kcnz (p less than 0.001). CLi decreased from 0.135 to 0.048 ml/min/gKW (p less than 0.001), and absolute proximal tubular reabsorption decreased from 0.877 to 0.508 ml/min/gKW (p less than 0.001), while the fractional reabsorption in the proximal tubule (FPR), expressed as a percentage of GFR, increased from 86.9 to 91.6% (p less than 0.005). Thus, after Kcnz treatment to rats given CyA 12.5 mg/kg/day, their renal function was indistinguishable from that in rats given CyA 25 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1986

Plasma concentrations of flunitrazepam (Rohypnol) following oral and sublingual administration.

Flunitrazepam (Rohypnol) 2.0 mg was given as a single dose by the oral or sublingual route to ten volunteers using a cross-over design. Plasma concentrations of the drug were measured by gas-liquid chromatography for up to 6 hours after administration. The highest mean concentration occurred 45 min after administration irrespective of route. No significant differences were found between the two treatments at any time. Since the sublingual route compares favorably with other routes of administration, these findings suggest that sublingual flunitrazepam is valuable for premedication.

Administration, Oral↗
PubMed1984

Intra-individual consistency of prednisolone kinetics during long-term prednisone treatment.

Eleven patients on long-term prednisone treatment were studied on two occasions separated by 45 to 325 days. In 10 patients the total body clearance of prednisolone only changed about 10%. In one case a 78.5% decrease was observed after stopping treatment with rifampicin and isoniazide. No association was found between the prednisone dose rate (mg/kg per month), patient age or mean endogenous plasma hydrocortisone level and prednisolone clearance/kg. The results indicate considerable intra-individual consistency of prednisolone kinetics if other conditions are not changed.

Adult↗
PubMed1984

Haemodynamic effects of intravenous procaine as a supplement to general anaesthesia in patients with valvular heart disease.

The effect of intravenous procaine, 2 mg/kg/min, on the cardiovascular function of nine patients scheduled for cardiac valve replacement was studied under enflurane-pancuronium anaesthesia. Procaine infusion was started after intubation during steady-state anaesthesia, and continued until start of cardiopulmonary by-pass. Systemic vascular resistance decreased steadily from 198.2 +/- 28.7 to 133.0 +/- 17.2 kPa X s/l (P less than 0.05). A simultaneous decline in mean arterial pressure from 10.13 +/- 0.68 to 7.47 +/- 0.48 kPa was observed (P less than 0.01). Cardiac index, heart rate, central venous pressure, pulmonary arterial mean pressure and pulmonary capillary wedge pressure were all unaffected by procaine as well as by surgical stimulation. It is concluded that continuous procaine infusion as an adjuvant to general anaesthesia effectively abolishes the hypertensive and tachycardiac response to surgical stimulation. The limiting factor in the amount of infused procaine appears to be the hypotension caused by vasodilation, not myocardial depression or convulsions.

Adjuvants, Anesthesia↗
PubMed1984

Steady state kinetics of pyridostigmine in myasthenia gravis.

We measured the fluctuations in plasma pyridostigmine concentration from day to day on 3 consecutive days and hour to hour during 1 day in 11 myasthenic patients, by studying their usual dosage regime. Plasma pyridostigmine was measured by gas chromatography/mass spectrometry. The intraindividual day-to-day variation in plasma pyridostigmine levels was small. A highly significant relationship was found between the oral pyridostigmine dose and the area under the plasma concentration/time curve. The bioavailability of oral pyridostigmine was 3.6%, estimated by replacing one dose with an intravenous dose amounting to 1/30 of the oral dose. The relatively stable kinetic behavior of pyridostigmine is in contrast to the interpatient variability in dose requirement, indicating that monitoring of plasma pyridostigmine levels should be reserved for special cases.

Administration, Oral↗
PubMed1982

Arterial and venous concentrations of phenobarbital, phenytoin, clonazepam, and diazepam after rapid intravenous injections.

Arterial and venous concentrations of phenobarbital, phenytoin, clonazepam, and diazepam were followed for 12 hr after a rapid intravenous injection. Initial blood samples were collected at intervals of only 5 sec. The arterial curves were initially much higher and steeper than the venous. For all four drugs the arterial curves could be described as triexponential functions. The initial part of the arterial curves were used in determining the initial supply to and uptake rate in the organs.

Anticonvulsants↗
PubMed1982

Controlled trials in epilepsy: a review.

A comprehensive review, evaluating 51 randomized double-blind controlled studies, covering different aspects of epileptology, is presented. Trials were grouped according to the investigated topic and for each group an attempt was made to derive an overall conclusion. The majority of studies investigated antiepileptic drug treatments. Other topics were: psychotropic effect of antiepileptic drugs, folic acid and vitamin D administration in epilepsy, and EEG investigations. A cross-sectional analysis of items such as designs, patient sampling principles, recording of effect parameters and side effects, concomitant treatments, and statistical evaluations demonstrated that cross-over designs, investigating fixed dosage schedules, were extensively used. Less than half of these studies included a washout period between treatments, complicating the interpretation of the obtained results. The vast majority of studies involved only chronic patients; and marked heterogeneity in patient selection with respect to age, seizure type, and mental status, and severity of epilepsy was observed. Classifications of seizures varied between the studies. The most prominent effect parameter was seizure frequency. The use of heterogeneous patient samples frequently necessitated equalization of widely different seizure types in order to perform statistical analyses. The mean duration of trials was 6 months, precluding evaluation of chronic toxicity. The majority of studies recorded side effects, but data collection was rather unsystematic and statistical evaluation was seldom applied. Most studies were add-on trials, and since concomitant treatment was frequently changed during the investigations, it was difficult to evaluate the influence of this variable. A correlation analysis across trials demonstrated, among other things, that the common assumption that short controlled trials provide too optimistic results, could not be substantiated. This survey provides no firm indication of which drug is more suitable for which seizure type.

Anticonvulsants↗
PubMed1982

5-aminosalicylic acid in a slow-release preparation: bioavailability, plasma level, and excretion in humans.

The release pattern, bioavailability, and kinetics of a 5-aminosalicylic acid tablet with sustained release were studied in humans. Six ileostomy patients received a single dose (500 mg). Eight and 48 h later, respectively, 58% and 65% of the dose was recovered in the ileostomy effluents, either as 5-aminosalicylic acid still retained in the preparation, free 5-aminosalicylic acid or acetyl-5-aminosalicylic acid. Fourteen healthy volunteers took 1500 mg of 5-aminosalicylic acid per day for 6 days and a steady state plasma acetyl-5-aminosalicylic acid concentration was reached on day 5 (1.1-2.9 microgram/ml). 5-Aminosalicylic acid was not detected in the plasma. At steady state, 40% of the 24-h dose was recovered from feces, and 53% from the urine. The sustained-release preparation studied provides sufficient amounts of 5-aminosalicylic acid to all parts of the gut and its curative effect in ulcerative colitis and Crohn's disease should be examined in controlled trials.

Adult↗
PubMed1981

Differences in single dose phenytoin kinetics between Greenland Eskimos and Danes.

Phenytoin (PHT) disposition was studied in Greenland Eskimos and in Caucasians (Danes) in order to reveal possible ethnic differences in the pharmacokinetics. PHT was administered i.v. as a single, subsaturation does to healthy adult volunteers and determined in plasma by thin-layer chromatography. Based on the time/concentration curves obtained, the half-life, volume of distribution, the area under the curve, and the total body clearance were calculated. The protein binding was measured by ultrafiltration. Three groups were studied: Group 1 were Eskimos living in East Greenland, group 2 were Eskimos living in Denmark, and group 3 were comparable Caucasians, as a reference group. The total body clearance of PHT per kg body weight was almost twice as high in Eskimos, irrespective of place of living or sex, compared with the Danish group. The volume of distribution was larger in the Eskimo group, but the protein binding did not differ. The reason for the differences in clearance and volume of distribution between the two ethnic groups is not clear, but the results emphasize that ethnic differences in pharmacokinetics can be of significance. The total body clearance values for PHT in Caucasians found in the present study agreed with results from other European investigations that used the same dose, but different analytical assays.

Adolescent↗