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Biomedical subjects

F Follath

Publications and source records attributed to F Follath.

At least 181 records · Page 10Linked to original sources
PubMed1984

[Prolonged coma caused by diazepam sedation in ventilated patients. Diagnostic and therapeutic use of the benzodiazepine antagonist Ro 15-1788].

Repeated administration of diazepam in two ventilated patients had caused drug cumulation and coma over several days. In both cases central nervous depression could be demonstrated by the benzodiazepin antagonist Ro 15-1788 which induced reversal of coma. Estimation of plasma concentrations in a 70-year-old female patient 150 hours after the last administration showed a diazepam concentration of 437 ng/ml and a desmethyl-diazepam concentration of 483 ng/ml. The calculated elimination half-life of these substances were 109 and 403 hours. In the second case benzodiazepin could be demonstrated in urine for 10 days after withdrawal of medication. These observations suggest that diazepam is not a suitable drug for prolonged sedation in artificially ventilated patients. The benzodiazepin antagonist Ro 15-1788 represents a valuable diagnostic aid in ascertained or suspect cases of benzodiazepin intoxications. It can also be used therapeutically for reversal of central nervous depression.

Aged↗
PubMed1984

Suppression of high-grade ventricular ectopic activity by antiarrhythmic drug treatment as a marker for survival in patients with chronic coronary artery disease.

In order to investigate the relationship between the ease of suppression of complex (frequent multiform, repetitive, and early) ventricular premature beats (VPBs) and subsequent survival, 50 consecutive patients with chronic coronary artery disease (CAD) were followed retrospectively during a mean observation period of 16 months. A total of 124 drug trials were performed using single or combined class I, II, and III antiarrhythmic drugs. Thirty-nine patients were considered "responders" (elimination of Lown classes greater than or equal to IVa and reduction of greater than 30 multiform VPBs to occasional unifocal VPBs during Holter monitoring), whereas in 11 patients VPBs could not be adequately suppressed ("nonresponders"). There were no significant differences in age and congestive heart failure in the two groups. There were three deaths (one sudden) in the 39 "responders" but five deaths (three sudden) in the 11 "nonresponders" (p less than 0.01 for all deaths, p less than 0.05 for sudden deaths). Cumulative probability of survival at 12 months was 0.93 for "responders" and 0.64 for "nonresponders" (p less than 0.005). Significant side effects necessitated drug withdrawal in four patients. Our data suggest that survival in patients with CAD is better when complex VPBs can be suppressed.

Adult↗
PubMed1984

Influence of thyroid function on theophylline kinetics.

Theophylline kinetics were examined in five patients with hyperthyroidism before and after treatment with carbimazole. Theophylline clearance fell after carbimazole, but the apparent volume of distribution did not change. There was a correlation between reduction in theophylline clearance and decreased thyroxine serum concentration. Data suggest that maximum induction is reached at a specific level of thyroxine beyond which no further increase in drug metabolizing activity takes place. In 15 subjects treated with aminophylline for acute bronchial obstruction, there was a positive correlation between thyroxine concentration and total body theophylline clearance (r = 0.72 for nonsmokers; r = 0.44 for smokers and nonsmokers).

Adult↗
PubMed1984

Experience with NONMEM: analysis of serum concentration data in patients treated with mexiletine and lidocaine.

The generality and flexibility of the computer package NONMEM also confront the user with the difficult task of choosing the model which best describes the data at hand. With two practical examples we show how one may proceed in building the population model for serum concentration measurements. Features of NONMEM are presented which help the user to make the choice among different models.

Computers↗
PubMed1984

[The choice of drugs and dosage for angina pectoris].

Nitrates, betablockers an calcium antagonists are the major drugs for treating angina pectoris. Therapeutic efficacy and incidence of unwanted reactions depend on the proper choice and dosage of these agents. The type of ischemic symptoms, cardiac function, presence of sinoatrial or atrioventricular conduction anomalies, and coexistent non-cardiac disorders should be taken into account when a particular drug is selected. In patients with angina at rest a calcium antagonist is indicated in the first place, while in exercise-induced ischemia betablockers and calcium antagonists are equally effective. With regard to antianginal efficacy there are no important differences between various representatives of these drug groups, but their tolerance may markedly vary in individual patients. Combination of betablockers, calcium antagonists and/or nitrates is often required in cases with severe limitation of exercise capacity. Therapeutic guidelines for patient groups with and without congestive heart failure are suggested.

Adrenergic beta-Antagonists↗
PubMed1984

Studies of the bioavailability of nitroglycerin from a transdermal therapeutic system (Nitroderm TTS).

In 6 healthy volunteers, intravenous infusions of nitroglycerin 4.8 and 10.6 micrograms/min yielded mean steady-state plasma concentrations of 0.5 +/- 0.02 and 0.82 +/- 0.04 ng/ml as determined by a gas chromatographic/mass spectrometric method. The plasma concentrations reached in the same subjects 17 h after application of Nitroderm TTS 5 and 10 with in vivo release rates of 3.7 and 5.7 micrograms/min were 0.28 +/- 0.01 and 0.37 +/- 0.01 ng/ml, respectively. Thus, 75% of the quantity of nitroglycerin released by the systems passed into the circulation. The inter-individual and intra-individual variations in plasma concentrations were similar for both modes of administration. The nitroglycerin-induced morphological changes in the fingerpulse wave were clearly dose-dependent, but it seems that this pharmacodynamic parameter is determined less by the plasma concentration than by the nitroglycerin content of the vascular wall.

Administration, Topical↗
PubMed1983

Cyclosporin A used alone or in combination with low-dose steroids in cadaveric renal transplantation.

The actual survival rate of 25 primary cadaveric kidney grafts in recipients treated initially with cyclosporin A (CyA) alone was 84%. The survival rate in 37 patients under conventional immunosuppression was 76%. The mean number of dialyses required in the first 4 weeks after transplantation was 1.2 per patient in both groups. At 15-28 months posttransplant, mean serum creatinine levels have remained stable at 175 mumol/l in the CyA group. The mean daily dose of steroids (including methylprednisolone i.v.) in the first two months was 2.07 mg/kg/d in patients under conventional immunosuppression and 0.76 mg/kg/d in the patients receiving CyA (p less than 0.001). The combination of CyA with low-dose steroids enabled the dose of CyA to be rapidly tapered off in once-weekly steps. CyA levels were monitored by determination of whole blood trough concentrations (target level: 300-800 ng/ml). At 60 days posttransplant the average dose of CyA was 6.0 +/- 0.5 mg/kg/d compared with an average daily dose of 11.4 +/- 0.9 as recommended for CyA alone in the protocol for the European multicentre study. This more rapid reduction in the CyA dose reduced nephrotoxicity (serum creatinine levels 174 +/- 14 as compared with 289 +/- 31 mumol/l) (p less than 0.05) and almost halved the number of methylprednisolone pulses given up to the end of the second month. We conclude from these results (1) that previously the dosage of CyA administered at this centre was probably too high, and (2) early adjustment of dose levels on the basis of blood concentrations and with low-dose prednisone cover appears to be safe and effective, but requires further verification.

Azathioprine↗
PubMed1983

Simultaneous determination of diprophylline, proxyphylline and theophylline in serum by reversed-phase high-performance liquid chromatography.

A selective and reliable high-performance liquid chromatographic assay for the simultaneous determination of diprophylline, proxyphylline and theophylline is described. The method involves a single extraction procedure followed by separation on an ODS reversed-phase column using a ternary solvent system. The assay is sufficiently rapid and sensitive to be applied for pharmacokinetic studies as well as for routine monitoring of patient's serum after therapeutic doses of the combined preparation. The practicability and utility of the proposed method is demonstrated in a pharmacokinetic study on four healthy volunteers.

Adult↗
PubMed1983

[Dangers of and indications for anti-arrhythmia therapy in the aged].

Preexisting anomalies of impulse formation and conduction, cardiac failure, myocardial ischemia and abnormal peripheral vasoregulation predispose the elderly patient to frequent and often severe side-effects of antiarrhythmic drugs. Paroxysmal supraventricular tachycardia in patients with sick sinus syndrome can be especially difficult to treat, as most antiarrhythmics further prolong the sinus node recovery time. Thus, implantation of a pacemaker is often necessary to prevent symptomatic bradycardia. Concomitant treatment with diuretics or digitalis also increases the risk of drug induced ventricular dysrhythmias. Interaction between quinidine, verapamil, amiodarone and digoxin may be the reason for drug toxicity. To compensate for decreased renal or metabolic drug clearances antiarrhythmic treatment in elderly patients should be initiated with lower doses than usual.

Aged↗
PubMed1983

The antiarrhythmic effects of controlled release disopyramide phosphate and long acting propranolol in patients with ventricular arrhythmias.

The antiarrhythmic effect of slow-release disopyramide phosphate (DR) 300 mg twice daily and of long-acting propranolol (PR) 1 X 160 mg daily was compared in a randomized cross-over study in patients with premature ventricular beats (PVB). 12 patients with PVB (Lown Classes II-V) were given: placebo I for 3 days, DR or PR for 7 days, placebo II for 5 days and PR or DR for 7 days. During each study phase Holter-ECG recordings were taken over a period of 24 h. With DR 6 patients showed a positive qualitative effect, improving by at least one Lown class, whereas only 2 patients did so with PR. With DR reduction of PVB greater than 80% occurred in 7 patients, and with PR in 2 patients. In all patients with any reduction in PVB, the median decrease was 85% with DR and 59% with PR. The overall results suggest that the antiarrhythmic effect of disopyramide phosphate in the slow-release preparation is at least satisfactory and comparable to that of disopyramide phosphate in the standard capsule formulation given in the usual and more complicated regime of four divided doses. The antiarrhythmic effect of PR in the recommended dose as given was not convincing.

Adolescent↗
PubMed1983

Intravenous cyclosporine kinetics in renal failure.

Kinetics of the novel immunosuppressive cyclosporine were determined in four patients with terminal renal failure. After a short intravenous infusion (2.05 to 3.5 mg/kg in 4 hr), blood and plasma concentrations were measured (HPLC and radioimmunoassay [RIA] up to 36 hr. After infusion, concentration curves of the drug were characterized by a rapid initial fall (t 1/2 alpha 0.10 +/- 0.03 hr), followed by a biphasic elimination phase with corresponding t 1/2s of 1.08 +/- 0.25 hr (t 1/2 beta) and 15.8 +/- 8.4 hr (t 1/2 gamma). The volumes of distribution, calculated from whole blood concentrations (HPLC), were 0.140 +/- 0.48 l/kg (volume of the central compartment) and 3.49 +/- 2.65 l/kg (volume of distribution at steady state), whereas systemic clearances were 0.369 +/- 0.08 l/hr/kg. Blood levels measured by RIA exceeded the HPLC values after the fourth hour by up to 100%, indicating the production of cross-reacting cyclosporine metabolites. Plasma concentrations were considerably lower than in whole blood. Elimination of unchanged cyclosporine in patients with renal failure appears to be of the same order as in those with normal kidney function. Modification of the initial dosage regimens is therefore probably not required.

Chromatography, High Pressure Liquid↗
PubMed1983

Cyclosporine in human bone marrow transplantation. Serum concentration, graft-versus-host disease, and nephrotoxicity.

Serum concentrations of cyclosporine were studied in 42 patients given cyclosporine for the prevention of graft-versus-host-disease (GVHD) following allogeneic bone marrow transplantation (BMT). Serum trough levels for cyclosporine were determined in each patient at least once weekly during the first 3 months and were compared with the occurrence of GVHD and with nephrotoxicity. Cyclosporine was given as 20 mg/kg i.m. or as a 24-hr infusion for the first 5-7 days. This was followed by a single daily oral dose of 12.5 mg/kg for 6 months. Cyclosporine was then gradually reduced and stopped after one year. After a median observation period of 2 years 25 of the 42 patients (59%) are alive. Twenty six patients (62%) developed GVHD, which was stage II or more in 11 (26%) and fatal in 2 patients (5%). Five patients developed GVHD 6-8 weeks after withdrawal of cyclosporine one year after BMT. All patients improved after restarting cyclosporine. No correlation between cyclosporine serum concentration and GVHD was observed, but patients with GVHD had greater fluctuations of their serum trough levels. Serum creatinine increased in all patients soon after BMT and was correlated with cyclosporine serum concentration during the first month. Serum creatinine, however, rose further despite lower cyclosporine concentrations in the second month. These results show that cyclosporine effectively reduces the severity, but not the incidence, of GVHD suggesting that there is a subset of cells resistant to cyclosporine. The therapeutic range, however, between high doses (which are often associated with nephrotoxicity) and the minimal effective dose of cyclosporine, has yet to be defined.

Adolescent↗