Inhibitory effect of N-nitro-

Assessing the value of health care interventions is more and more a concern of governments, clinicians, health insurance companies, policy makers, and the general public. One dimension of the outcomes of such interventions that has received relatively little attention until recently is quality of life. However, during the last decade, measuring quality of life has become more frequent. Methodologies have also developed rapidly. At the same time, methodological problems continue to be troubling. In part, this explains the relative lack of use of validated measures of quality of life in clinical trials. In the future, measuring quality of life will certainly become more frequent. It may even be demanded by policy making bodies. Increasingly, too, economic costs will be part of such studies. This requires considering both clinical and economic data.     

Effects of nitric oxide donors on basal and K-evoked release of

Assessing the value of health care interventions is more and more a concern of governments, clinicians, health insurance companies, policy makers, and the general public. One dimension of the outcomes of such interventions that has received relatively little attention until recently is quality of life. However, during the last decade, measuring quality of life has become more frequent. Methodologies have also developed rapidly. At the same time, methodological problems continue to be troubling. In part, this explains the relative lack of use of validated measures of quality of life in clinical trials. In the future, measuring quality of life will certainly become more frequent. It may even be demanded by policy making bodies. Increasingly, too, economic costs will be part of such studies. This requires considering both clinical and economic data.     

Inactivation of nitric oxide synthases and cellular nitric oxide formation by N-iminoethyl-

Assessing the value of health care interventions is more and more a concern of governments, clinicians, health insurance companies, policy makers, and the general public. One dimension of the outcomes of such interventions that has received relatively little attention until recently is quality of life. However, during the last decade, measuring quality of life has become more frequent. Methodologies have also developed rapidly. At the same time, methodological problems continue to be troubling. In part, this explains the relative lack of use of validated measures of quality of life in clinical trials. In the future, measuring quality of life will certainly become more frequent. It may even be demanded by policy making bodies. Increasingly, too, economic costs will be part of such studies. This requires considering both clinical and economic data.     

Quality of life 1 Perspectives

Assessing the value of health care interventions is more and more a concern of governments, clinicians, health insurance companies, policy makers, and the general public. One dimension of the outcomes of such interventions that has received relatively little attention until recently is quality of life. However, during the last decade, measuring quality of life has become more frequent. Methodologies have also developed rapidly. At the same time, methodological problems continue to be troubling. In part, this explains the relative lack of use of validated measures of quality of life in clinical trials. In the future, measuring quality of life will certainly become more frequent. It may even be demanded by policy making bodies. Increasingly, too, economic costs will be part of such studies. This requires considering both clinical and economic data.     

Quality of life 3 Rheumatoid arthritis

It has increasingly been recognized that for the evaluation of interventions in patients with rheumatoid arthritis not only physician-oriented variables, like laboratory or radiographic assessments but also patient-oriented variables such as quality of life are of importance. Many different arthritis-specific quality of life instruments have been developed in recent years using different or no definition at all about the concept quality of life. In this review a generally accepted definition of quality of life, existing of three components, is presented. The interrelationship between quality of life and all the different variables used in assessing disease activity in rheumatoid arthritis is discussed.     

Acitretin (Neotigason?) A review of pharmacokinetics and teratogenicity and hypothesis on metabolic pathways

Acitretin was introduced as a replacement for etretinate, the ethyl ester of acitretin. Acitretin is eliminated at a much faster rate than etretinate. Although both drugs are teratogens, the replacement was important especially as it allowed for a much shorter post-medication period in which pregnancy should be precluded. Recent findings showed the presence of etretinate in the plasma of acitretin-treated patients. This article gives a review of known metabolic pathways of the retinoids and tries to elucidate the possible conversion of acitretin into etretinate after acitretin ingestion.     

Oxidative stress Biochemistry and human disease

The early involvement of free radicals in the evolution of life may explain their ubiquitous presence and vital physiological role. Imbalance between protection against free radicals and their generation, explains the likely association of various diseases with toxic oxygen species. An elaborate defence system against oxygen-free radicals exists. The effects of oxidative stress are manifold. Direct demonstration of oxygen radicals in intact biological systems is difficult. Frequently, effect-related measurements are used in this respect. The clinical conditions adult respiratory distress syndrome and multiple organ failure, reflex sympathetic dystrophy and sugar cataract are discussed and the role of oxygen radicals in the aetiology of these diseases are described.     

Nitrattoleranz Ein Problem der chronischen Nitrattherapie

Die organischen Nitrate stellen in der Therapie von Patienten mit Angina pectoris effektive Wirkstoffe dar. Bei der Behandlung akuter Episoden der Angina pectoris sind sie die Mittel der Wahl. Darüber hinaus sind sie auch bei der Angina-Prophylaxe von Nutzen. Während die organischen Nitrate bei der Angina-Prophylaxe im Rahmen der Akuttherapie überaus wirksam sind, gibt es zunehmend Hinweise, daß sich bei mehrmaliger Dosierung für die orale und auch transdermale Therapie eine wesentliche Minderung der antianginösen Effekte entwickelt. So verbessert sich nach Anwendung organischer Nitrate bei der akuten Therapie die Belastungstoleranz für viele Stunden. Bei der Dauertherapie hingegen, die während einer Periode von 24 Std einen antianginösen Schutz gewährleisten soll, kommt es zu einer deutliche Einbuße in der Wirksamkeit. Wie gezeigt wurde, können Behandlungskonzepte, die eine wash-out-Phase für das Nitrat beeinhalten, die Nitrattoleranz verhindern oder rückgängig machen. Dennoch gewährleisten diese Konzepte einen andauernden antianginösen Schutz. Es bestehen keine Zweifel, daß das Ziel eines gleichmäßig andauernden antianginösen Schutzes während 24 Std durch Einsatz der organischen Nitrate nicht erreicht werden kann. Mit angemessenen Dosierungsschemata ist es aber möglich, die Belastungstoleranz in der entscheidenden Phase eines 24 Std-lntervalls zu verbessern.     

Controlling cancer chemotherapy-induced emesis An update

Cytotoxic chemotherapy can induce acute, delayed and anticipatory nausea and vomiting. The efficacy and toxicity data of the available anti-emetics and their role in chemotherapy-induced emesis are reviewed. Moreover, some pitfalls in the methodology of anti-emetic trials as well as factors known to affect the individual sensitivity of patients for the emetic challenge are illustrated. So far, high-dose metoclopramide (3–6 mg·kg^–1·d^–1) was the most effective single agent in the control of acute emesis. However, extrapyramidal reactions caused by its dopamine antagonism remained a major drawback. The addition of dexamethasone and/or lorazepam decreases the incidence of extrapyramidal reactions, and further improves anti-emetic control. In animals, serotonin type 3 receptor antagonists have demonstrated promising anti-emetic results against chemotherapy-induced and radiotherapy-induced emesis; the results of clinical studies are awaited. Delayed nausea and vomiting have not been studied as extensively. At present, the combination of metoclopramide and dexamethasone offers an optimal protection in approximately 50% of patients on cisplatin chemotherapy. Anticipatory nausea and emesis remain major problems, and an effective pharmacological treatment is lacking. Attempts to control this type of emesis focus on drugs with amnesic properties and on behaviour therapy.     

Possibilities of continuous care Part I

The continuity of health care in the Netherlands is hampered by its structure. There exists a sharp border between the first echelon in which the primary general care is given and the higher echelons in which the out-patient and hospital care is delivered. The policy of the Government is directed to substitution of out-patient and hospital functions, executed in primary care. The possibilities and difficulties for patients and pharmacists are discussed.     

Aminoglycoside therapy Current use and future prospects

The microbiological, pharmacokinetic, toxicological and clinical aspects of aminoglycosides are reviewed. Aminoglycosides still have an important place in serious infections in neutropenic patients, endocarditis andPseudomonas aeruginosa infections, all in combination with beta-lactams. Monotherapy (with streptomycin) is indicated in less common diseases like tularaemia and bubonic plague. Several experimental studies support a oncedaily dosing regimen for aminoglycosides (comparable or better efficacy with less ototoxicity and nephrotoxicity). Only a very limited number of prospective comparative studies have been performed, and much more data on efficacy, development of resistance and toxicity is needed before once-daily administration can be recommended. The choice of an aminoglycoside should be based primarily on the local sensitivity patterns and cost. Differences in ototoxicity and nephrotoxicity are usually minor. If the acquisition costs of amikacin decline, it is to be expected that amikacin will be the aminoglycoside of choice.     

Teicoplanin in perspective A critical comparison with vancomycin

Teicoplanin is a new glycopeptide antibiotic with a chemical structure related to vancomycin. The proposed advantages of teicoplanin over vancomycin are discussed. These include lower incidence of side-effects, lower toxicity (especially in combination with aminoglycosides), lower dosage frequency and the possibility of intramuscular administration. There is only a limited number of studies comparing both agents; more studies are still needed before firm conclusions can be drawn. Therapeutic drug monitoring is not usually necessary for teicoplanin; the situation is not clear for vancomycin. There is some doubt whether the incidence of resistance is as infrequent for teicoplanin as it is for vancomycin. Teicoplanin appears to be a promising alternative to vancomycin, but more data are needed on the relative clinical efficacy and the development of resistance to both drugs.     

Nitrate tolerance A problem during continuous nitrate administration

The organic nitrates are effective agents in the management of patients with angina pectoris. They are the agents of choice in the treatment of acute episodes of angina pectoris and are useful in angina prophylaxis. While the organic nitrates are extremely effective in angina prophylaxis during acute therapy, there is increasing evidence that with many dosing regimens for oral and transdermal therapy, substantial attenuation of the antianginal effects develops. Thus, during acute therapy the organic nitrates improve exercise tolerance for many hours, but during sustained therapy designed to provide antianginal efficacy throughout the 24-h period there is significant attenuation of the beneficial effects. It has been documented that treatment regimens designed to provide a period of nitrate washout prevent or reverse nitrate tolerance, and such changes in dosing regimens have been shown to provide continued antianginal protection. It is clear that the objective of providing 24-h antianginal protection with the organic nitrates cannot be achieved. With appropriate dosing schedules, however, it is possible to improve exercise tolerance throughout the major portion of the 24-h dosing period.     

Oxytocics for the prevention of post-partum haemorrhages A review

Secale alkaloids, oxytocin and prostaglandins are used to prevent post-partum haemorrhage (post-partum haemorrhage defined as blood loss 500 ml). Any oxytocic drug administered in the third stage of labour reduces the blood loss with approximately 40% and hence the incidence of post-partum haemorrhage from 10 to 6%. Therefore, routine active management of the third stage with an oxytocic drug is strongly advocated. Because of the fewest side-effects oxytocin is regarded as the best drug available at this moment.     

Pharmacology of long-term potentiation A model for learning reviewed

Long-term potentiation is widely used as a model for memory formation. Recently, much information concerning this topic like the involvement of protein kinase C, arachidonic acid andN-methyl-d-aspartate receptors has been reported. In this review recent discoveries concerning long-term potentiation and the pharmacological implications for the development of cognition-enhancing drugs are discussed.     

Fluoroquinolones Adverse reactions during clinical trials and postmarketing surveillance

The knowledge of side effects of fluoroquinolones during clinical trials and postmarketing surveillance is reviewed. Gastro-intestinal side effects (observed in 3–6% of the patients) are the most frequently observed side effects followed by side effects of the central nervous system (0.5–1.5%) and skin reactions (0.5–2%). The incidence of severe side effects is very low and most effects can be reserved rapidly upon discontinuation of therapy. Reactions of the central nervous system (sometimes severe) were the most often spontaneously reported events during the postmarketing surveillance of ofloxacin. The incidence of adverse reactions is usually in the same range as that of other antimicrobial agents like the third generation cephalosporins, imipenem and aztreonam. Fluoroquinolones are usually well-tolerated and safe drugs, but more data is needed on the long-term safety of quinolones, the safety in children, in elderly people and in severely ill patients.