[Unstable angina pectoris: distress signal in coronary heart disease].
Explore the source record for details and available documents.
Angina, Unstable↗
Biomedical subjects
F Follath
Publications and source records attributed to F Follath.
In vitro inhibition of midazolam and quinidine metabolism by flavonoids.
Studies in humans in vivo have demonstrated that substances found in grapefruit juice may increase the bioavailability of dihydropyridine derivatives as a result of the inhibition of liver enzyme activities by flavonoids found in grapefruit. Since the metabolism of dihydropyridine drugs is mediated by cytochrome P-450 (CYP) 3A4, it has been hypothesized that flavonoids may also influence the metabolism of other drugs, such as midazolam and quinidine, which are biotransformed by the same CYP isoform. Three flavonoids, kaempferol, naringenin and quercetin, are found in grapefruit juice but not in orange juice. The effect of these substances on the metabolism of midazolam and quinidine has been investigated in human liver microsomes. In the concentration range 10-160 microM the inhibitory potential of flavonoids was the same for both of the tested drugs; it decreased in the order quercetin >> kaempferol > naringenin. The data suggest that the flavonoids found in grapefruit juice may influence the kinetics of midazolam and quinidine in man.
Anti-Arrhythmia Agents↗
Multicenter quality control study of amikacin assay for monitoring once-daily dosing regimens. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.
During once-daily dosing regimens of aminoglycosides, administration of large single doses results in high peak levels and low 24-h trough levels. However, commercial assays for monitoring aminoglycoside levels are designed to cover the smaller range of serum concentrations usually observed during multiple daily dosing regimens. The study assessed (a) the range of serum concentrations during once-daily dosing of amikacin and (b) the performance of a widely used assay system for measuring concentrations within this range. A total of 42 dosing intervals from eight patients receiving a once-daily regimen of amikacin (20 mg/kg) were monitored. Median (and range) of peak, 8- and 24-h trough levels were 61 (25-89), 5.9 (2.2-19), and 1.3 (< 0.8-6.2) mg/L, respectively. The accuracy of a fluorescence polarization immunoassay for measuring concentrations of amikacin during once-daily dosing regimens was assessed in an international multicenter study. The performance of the assay was excellent for peak and 8-h concentrations; median deviations from the target concentrations were < 5%. The majority of the trough levels (26 of 42) measured in patients during once-daily treatment were within the range of 1-2 mg/L and could also be determined with an accuracy sufficient for clinical monitoring (median deviations 14%).
Adult↗
Metabolism of theophylline by cDNA-expressed human cytochromes P-450.
1. Theophylline metabolism was studied using seven human cytochrome P-450 isoforms (CYPs), namely CYP1A1, 1A2, 2A6, 2B6, 2D6, 2E1 and 3A4, and microsomal epoxide hydroxylase (EH), expressed in human B-lymphoblastoid cell lines. 2. At a high theophylline concentration of 10 mM four CYPs (1A1, 1A2, 2D6, 2E1) catalyzed the metabolism of theophylline. 3. Theophylline had the highest affinity (apparent Km range 0.2-1.0 mM) for the CYP1A subfamily and the kinetics of metabolic formation mediated by CYP1A2 indicated substrate-inhibition (Ki range 9-16 mM). 4. CYP1A2 catalyzed the demethylation of theophylline as well as its hydroxylation, and was associated with the highest intrinsic clearance (1995 l h-1 per mol CYP) to 1,3-dimethyluric acid (DMU). Therefore, this isoform can be considered to be the most important enzyme involved in theophylline metabolism in vitro. 5. CYP2E1 was responsible for a relatively high intrinsic clearance by 8-hydroxylation (289 l h-1 per mol CYP). The apparent Km value of this reaction was about 15 mM, suggesting that CYP2E1 may be the low-affinity high-capacity isoform involved in theophylline metabolism. 6. The affinity of theophylline for CYP1A1 was comparable with that of its homologue 1A2. When induced, the participation of CYP1A1 in theophylline metabolism may be important. 7. CYP2D6 played only a minor role and CYP3A4 was not active in the in vitro metabolism of theophylline. 8. Our findings confirm the major role of CYP1A2 in theophylline metabolism and explain why in vivo the elimination kinetics of theophylline are non-linear and in vitro theophylline metabolism by human liver microsomes does not obey monophasic kinetics. 9. The data suggest also that not only tobacco smoking but also chronic alcohol intake may influence theophylline elimination in man as ethanol induces CYP2E1.
Alcohol Drinking↗
Cyclosporine treatment of severe ulcerative colitis during pregnancy.
Explore the source record for details and available documents.
Adult↗
[Type and frequency of severe infectious complications in the treatment of acute leukemia. Prospectively acquired findings in a consecutive patient cohort].
139 patients with newly diagnosed acute leukemia were admitted to our institution from 1984 to 1990. More than 70% developed severe infections during cytotoxic chemotherapy. Septicemia accounted for 40.1%. The two most frequent organisms isolated from the blood were Staphylococcus epidermidis and E. coli. A prominent finding were the soft tissue infections (23.4%). They often occurred in the anorectal area and at the exit of an intravenous catheter. Pneumonia (17.8%) was of fungal origin in 22.9%. 66% of the infections occurred when the neutrophils were below 100/microliters.
Antineoplastic Combined Chemotherapy Protocols↗
[Cyclosporin in autoimmune diseases].
At a symposium held in Zurich in November 1993, a series of presentations covered the optimal use of cyclosporin A (CsA) in autoimmune diseases. Besides its immunosuppressive effects in organ transplantation, CsA appears to be active in a variety of autoimmune disorders. Its most pronounced and beneficial clinical effects are seen in patients with severe rheumatoid arthritis. New clinical studies include the nephrotic syndrome in children and patients with systemic lupus erythematodes. The main concern remains CsA induced nephrotoxicity. For the treatment of autoimmune disorders CsA can be used at lower doses (< or = 5 mg/kg per day) than in transplantation medicine. Thus, monitoring of CsA blood concentrations is not usually necessary. The galenics of CsA has been optimized recently, an achievement which will further improve the clinical use of CsA. Due to increased knowledge of intracellular CsA binding proteins and of effects of CsA on T-lymphocytes and cytokine production, it can be expected that novel immunosuppressive compounds will be developed.
Adult↗
Infectious complications in 100 consecutive heart transplant recipients.
Clinical and laboratory data on infectious complications in 100 consecutive heart transplant recipients were analyzed retrospectively. The mean length of follow-up was 651 +/- 466 days. All patients received a basic immunosuppressive regimen including cyclosporine (whole blood target trough level 400-600 micrograms/l), azathioprine (1 mg/kg/day) and prednisone (0.15 mg/kg/day). Early rejection prophylaxis consisted of polyclonal rabbit antithymocyte globulin (ATG) (4 mg/kg/day for 4 days) in the first 57 patients and monoclonal murine OKT-3 (5 mg/day for 14 days) in the remaining patients. The primary cause of death was infection in three patients and rejection in 16 (p < 0.001). The incidence of infection was 0.96/patient/year (n = 179); 95 infections were nosocomial (53%), 47 community-acquired (26%) and 37 opportunistic (21%). The number of hospitalizations due to infections was fewer than that due to rejection (53 versus 246 respectively, p < 0.0001), but the mean length of hospital stay was longer in the first group (13.85 +/- 10.92 days versus 3.48 +/- 2.28 days, p < 0.001). Previous early rejection prophylaxis with OKT-3 was associated with a greater number of opportunistic and nosocomial infections compared to prophylaxis with ATG (p < 0.05), as was treatment with ATG and steroid pulses compared to steroid pulses alone in cases of opportunistic infection (p < 0.05).
Adult↗
Determination of piroximone in human plasma by high-performance liquid chromatography.
A rapid and selective high-performance liquid chromatographic (HPLC) method using solid-phase extraction (SPE) for measuring piroximone in plasma samples has been developed. Human plasma and internal standard were pipetted onto a Bond Elut C18 extraction cartridge conditioned with methanol and water. Impurities and proteins were washed out with water. Piroximone and internal standard were eluted with methanol. After evaporation, the residue was dissolved in the mobile phase and the aliquot injected into the HPLC system. Piroximone and its related compounds were separated on a reversed phase C18 HPLC column maintained at 50 degrees C using a mobile phase consisting of phosphate buffer and methanol. Piroximone-N-oxide, piroximone, and internal standard were detected spectrophotometrically at 340 nm. The extraction recovery for piroximone was 94%. The within- and between-run coefficients of variation were < 3% in the concentration range of 320-5,000 ng/ml and < 17.5% at lower concentrations, e.g., 20 ng/ml. The limit of detection was 10 ng/ml.
Calibration↗
Plasma triglycerides and three lipoprotein cholesterol fractions are independent predictors of the extent of coronary atherosclerosis.
BACKGROUND: The lipoprotein system has manifold links to atherosclerotic disease. LDL cholesterol is related to lesion formation and growth. The cholesterol of HDLs is indicative of protection against atherosclerosis. The status of triglycerides and of subfractions of high-density lipoproteins as risk factors is less certain. Also, the magnitude of the atherogenic/protective power of these factors is not known. METHODS AND RESULTS: Five hundred patients (418 men and 82 women) were enrolled in an angiographic study. A total of 1006 coronary lesions with > or = 50% narrowing were recorded as study end points. By extent of atherosclerosis, defined as the number of > or = 50% lesions, the study subjects were allocated to one of four ordered categories with 0, 1 to 3, 4 to 6, or 7 to 10 lesions, respectively. Subfractions of HDL cholesterol were determined by a dual precipitation method. By a polychotomous logistic regression model, it was found that, besides age and sex, LDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, and triglycerides were independently predictive (P < .05) of the extent of coronary atherosclerosis. An increase in age by 10 years was associated with an increase of the odds ratio for falling into a higher-extent category by a factor of 1.64, and the same increase of the odds ratio was obtained by increasing LDL cholesterol by 0.92 mmol/L or triglycerides by 1.01 mmol/L and by decreasing HDL2 cholesterol by 0.20 mmol/L or HDL3 cholesterol by 0.46 mmol/L. The less sensitive coronary end point, presence of atherosclerosis (ie, observation of > or = 1 lesion of > or = 50%) depended significantly on age, sex, LDL cholesterol, and HDL2 cholesterol, but not on HDL3 cholesterol or triglycerides. CONCLUSIONS: In addition to LDL, HDL2, and HDL3 cholesterol, triglycerides also proved independently predictive of the extent of coronary atherosclerosis.
Cholesterol, HDL↗
Cavernous destruction of an upper lung lobe in a healthy young man. An unusual roentgenographic presentation of allergic bronchopulmonary aspergillosis.
We describe a 32-year-old man with no history of pulmonary disease who presented with extensive cavernous destruction of the right upper lobe as an incidental finding on a chest x-ray film. All major criteria of allergic bronchopulmonary aspergillosis (ABPA) were present. Histologic examination of the resected lobe showed the typical features of ABPA. The differential diagnosis of multiple cavitating lesions should include ABPA.
Adult↗
[Toward purposeful prevention. Interview by Klaus Reinhardt].
Explore the source record for details and available documents.
Cardiovascular Diseases↗
[Primary prevention of coronary heart disease with drugs: wishful thinking or reality?].
The primary prevention of coronary artery disease remains a controversial issue. Beside the much disputed lipid-lowering drugs we have additional possibilities for a pharmacological intervention, such as the administration of antioxidants (e.g. vitamin E), aspirine or estrogens. In this article the epidemiological data with such treatments are presented. In selected populations the relative risk of cardiovascular events could be reduced 40 to 60% by vitamin-E supplements, low-dose aspirine and estrogen replacement in postmenopausal women. The protective effects are most marked in persons over 50 years with coexistent cardiovascular risk factors. There are, however, also potential dangers of a primary prophylaxis by drugs, such as the increased risk of cerebral and gastrointestinal hemorrhage with aspirine or the induction of endometrial carcinoma or breast cancer with estrogens. For this reason dietary and life style counselling should remain the most important measure in primary prophylaxis. In individuals with cardiovascular risk factors--which should be eliminated, if possible--additional administration of aspirine, estrogens or antioxidants may be considered after a careful evaluation of the overall risk/benefit ratio.
Antioxidants↗
[Possibilities of catheter therapy in vascular stenosis, vascular abnormalities, tumors and hemorrhages. Synopsis of an interdisciplinary colloquium].
Modern interventional catheter-technics allow amelioration of arterial blood flow by dilatation of narrowed or recanalization of closed coronary and peripheral arteries. Patients with chronic or unstable angina pectoris not responding to therapy can thus be treated successfully by percutaneous dilatation (PTCA). In peripheral occlusive disease balloon catheterization sometimes in combination with local fibrinolysis and thrombectomy may prevent amputation. On the other hand, cerebral malformations of arteries, aneurysms and tumors can be eliminated by artificial occlusion. Therapeutic embolization is also increasingly used in acute or recurrent haemorrhage in lungs, spleen and gastrointestinal tract. It may also be used as palliating therapy in malignancies. Medical indications and limitations of the various catheter techniques in cardiology, angiology, neurology and interventional radiology are discussed.
Angioplasty, Balloon↗
[Therapy of hyperlipoproteinemia].
Triglycerides and cholesteryl esters are non-polar molecules and, therefore, insoluble in aqueous fluids such as blood. Lipid transport in blood is only possible the formation of lipoproteins. This article proposes a concept for the treatment of hyperlipidemias that is based on lipoprotein pathology. The liver secretes the triglycerides and cholesteryl esters in the form of very-low-density lipoproteins (VLDL). Lipolysis hydrolyzes VLDL triglycerides, providing tissues with fatty acids. and gives rise to relatively cholesterol-enriched intermediate-density lipo- proteins (IDL) and low-density lipoproteins (LDL). IDL and LDL are removed from plasma by receptor-mediated cellular uptake. An increased plasma concentration of VLDL ensues in predominant hypertriglyceridemia (e.g. triglycerides 9 mmol/l, cholesterol 7 mmol/l). VLDL are not considered to be directly atherogenic, but increased levels of VLDL often occur together with an atherogenic decrease of high-density lipoproteins (HDL). Elevated VLDL levels respond well to dietary measures; fibric acid derivatives, nicotinic acid and omega-3-fatty acids also effectively lower VLDL. An increase in IDL leads to both hypertriglyceridemia (e.g. 3 mmol/l) and hypercholesterolemia (e.g. 7 mmol/l). IDL are considered directly atherogenic. Hyperlipidemias due to IDL respond to the same interventions as those due to VLDL. An increased blood level of LDL leads to hypercholesterolemia (e.g. 7 mmol/l) with normal triglyceride levels (e.g. 1 mmol/l); LDL are considered directly atherogenic. Dietary measures can reduce LDL levels by about 10%, but pharmacological treatment by inhibitors of cholesterol synthesis ('statins') and by ion exchange resins is much more effective.(ABSTRACT TRUNCATED AT 250 WORDS)
Anticholesteremic Agents↗
Hemodynamic effects and concentration-effect relationship of a graded infusion of piroximone in patients with severe heart failure.
Piroximone is a new phosphodiesterase III inhibitor that combines inotropic and vasodilator properties. To elucidate the optimal dose regimen and the dose-concentration-effect relationships, we studied eight patients with congestive heart failure of New York Heart Association class IV during a continuous multistage infusion over a 24-h period followed by a 4-h washout. After a bolus of 0.5 mg/kg, infusions at a rate of 2.5, 5.0, and 10.0 micrograms/kg/min for 8 h each were given to determine the maintenance dose of piroximone required to achieve an increase in cardiac index > or = 30%. Serial assessment of hemodynamics, plasma piroximone levels, and ventricular ectopic beats was performed. Following the loading dose and at higher infusion rates (5 and 10 micrograms/kg/min) Piroximone produced significant hemodynamic changes compared to baseline, i.e., a maximum increase in cardiac index from 2.2 +/- 0.4 to 3.6 +/- 0.8 L/min/m2 (67 +/- 21%), decreases in right atrial pressure from 14 +/- 3 to 9 +/- 3 mm Hg (40 +/- 16%), pulmonary capillary wedge pressure from 29 +/- 5 to 23 +/- 7 mm Hg (28 +/- 18%), pulmonary vascular resistance from 249 +/- 93 to 151 +/- 59 (45 +/- 19%), and systemic vascular resistance from 1,330 +/- 442 to 752 +/- 272 dyn s/cm5 (44 +/- 19%). Piroximone increased the heart rate by 10% at the highest dose and produced a decrease in mean arterial pressure by 13%. There was a slight increase in ventricular ectopy in two patients (2.2 and 3 VPBs/min) and no change in the remaining six.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Drug therapy of heart failure].
The amelioration of symptoms and the improvement of long-term prognosis are the main objectives of drug treatment in congestive heart failure [CHF]. Digitalis, glycosides and diuretics can reduce dyspnea and increase exercise tolerance, while their influence on the course of the cardiac failure remains uncertain. Vasodilators, ACE inhibitors in particular, have in contrast not only the desirable symptomatic and hemodynamic effects, but they also delay the deterioration of LV dysfunction and reduce cardiac mortality. Vasodilators, therefore, became first-line drugs in all stages of CHF. In patients with moderate to severe heart failure the addition of diuretics and also of digoxin is usually required. Pharmacological effects, dosage, side effects and specific indications of the various drug groups in CHF are discussed.
Cardiotonic Agents↗
[Therapy of atrial fibrillation with class III anti-arrhythmia agents].
Medical treatment of atrial fibrillation has been carried out most frequently with digoxin, quinidine, propafenone or flecainide. In spite of unequivocal efficacy, the use of class I antiarrhythmic agents is the subject of considerable controversy. In addition to increased mortality in patients with ventricular arrhythmias after myocardial infarction, proarrhythmic effects with flecainide have also been described in patients with supraventricular arrhythmias. A meta-analysis of long-term treatment of atrial fibrillation with quinidine disclosed that the mortality in those treated with quinidine at 2.9% was significantly higher than those receiving placebo at 0.8%. In consideration of the prevailing uncertainty with the use of class I antiarrhythmic agents, class III antiarrhythmic drugs such as sotalol and amiodarone have been administered for supraventricular arrhythmias with increasing frequency. Treatment of atrial fibrillation with sotalol Sotalol is a noncardioselective beta-adrenergic receptor blocker with antiarrhythmic properties of class III. This drug prolongs the duration of the action potential and the refractory periods in atrial and ventricular myocardium and slows the AV-conduction as well as the sinus node rate. On oral administration, there is good resorption and a half-time of seven to 18 hours. The effective oral dose varies between 80 and 320 mg/12 hours. For conversion of acute supraventricular arrhythmias, an i.v. bolus of 0.5 to 1.5 mg/kg has been used. The results of clinical studies with sotalol in the treatment of atrial fibrillation are shown in Table 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Amiodarone↗