Lege Artis Medicinae

[Compounds – Plants...]

GRÉTSY Zsombor

JULY 20, 2006

Lege Artis Medicinae - 2006;16(07)

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Lege Artis Medicinae

[NONINVASIVE MECHANICAL VENTILATION IN CHRONIC OBSTRUCTIVE LUNG DISEASES WITH ACUTE OR CHRONIC RESPIRATORY FAILURE]

BALIKÓ Zoltán

[Over the past decade, the use of noninvasive ventilation in the setting of acute exacerbations of chronic obstructive pulmonary disease (COPD) has gained popularity, and is recommended by evidence-based guidelines. The evidence that it should be effective in chronic COPD is much weaker, and large, prospective, randomised, controlled studies that would also provide a guide for the selection of the best candidates, are still lacking. It has bee established, however, that home mechanical ventilation is certainly beneficial for a well-defined subgroup of patients. This includes the so called “blue bloater” patients (with hypercapnia and polyglobulia), other cases with increased hypercapnia, and patients with "overlapping" syndrome (COPD accompanied by sleep apnoe). Also, for patients with acute respiratory failure who refuse intratracheal intubation noninvasive mechanical ventilation remains the only choice. The past years have unequivocally proved the superiority of the positive pressure ventilation mode for either short term or long term use.]

Lege Artis Medicinae

[Interdisciplinary forum of MOTESZ - Budapest, 23-25th March, 2006.]

KRAMER Imre

Lege Artis Medicinae

[ACTINOMYCOSIS MIMICKING LUNG CANCER]

CSERNI Gábor, BORI Rita, BOROSS Gábor, FRANK Emil, LÓRÁND Katalin, SERÉNYI Péter, LENGYEL Mária, KOVÁCS Károly, HALÁSZ Mátyás

[INTRODUCTION - The mortality of lung cancer is high, but with early diagnosis the disease can often be cured. The differential diagnosis of pulmonary carcinoma is widely diverse. CASE REPORT - In a 53-year-old male patient, who had been successfully treated for pneumonia complicated with thoracic empyema, both a CT scan and bronchoscopy raised the suspicion of a malignant tumour. Brush cytology was inconclusive; it raised the possibility of malignancy but was not felt diagnostic of a malignant process, whereas biopsy revealed only inflammatory changes. After right lower lobectomy, actinomycosis was diagnosed by histology. This case is used in the paper as an opportunity to discuss the pseudotumorous presentation of thoracic actinomycosis. CONCLUSION - Pulmonary and thoracic actinomycosis is rare, but due to its ability to simulate tumours, it is an important disease to consider in the differential diagnosis of lung cancer.]

Lege Artis Medicinae

[THE POTENTIAL ROLE OF THE SEMICARBAZIDESENSITIVE AMINE OXIDASE ACTIVITY IN THE DEVELOPMENT OF DIABETIC RETINOPATHY]

DURA Eszter

[Recent data suggest that the copper-containing semicarbazide-sensitive amine oxidase enzyme (SSAO) may play a role in vascular endothelial damage through conversion of certain endogenous monoamines, such as methylamine, into cytotoxic aldehydes, hydrogen peroxide and ammonia. SSAO is present in various human tissues and in the serum. Elevated SSAO activities have been reported in patients with both types of diabetes mellitus. We have demonstrated that the activity of serum SSAO is significantly higher in type 2 diabetic patients with high-risk proliferative diabetic retinopathy compared to those without retinopathy. Our clinical results support the hypothesis that elevated SSAO activity may be involved in the pathogenesis of microvascular diabetic late complications, such as retinopathy. The enzymatic conversion of the endogenous monoamines (e.g. methylamine, aminoacetone) into toxic aldehydes and hydrogenperoxide may be one of the possible mechanisms of the development of microangiopathy. Also, the vascular adhesion protein-1 (VAP-1) function of the molecule can cause leukostasis and leukocyte activation through increased leukocyte adhesion, resulting in worsening of the capillary circulation and hypoxia. Further prospective, larger studies are needed to elucidate the role of the possible association between serum SSAO activity and highrisk proliferative retinopathy in patients with type 2 diabetes. The pharmacological manipulation of SSAO activity might be an interesting new concept for prevention and treatment of diabetic retinopathy.]

Lege Artis Medicinae

[In the focus: periferal vascular diseases - Readers’ questions answered by dr. Éva Meskó]

MESKÓ Éva

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Lege Artis Medicinae

[New possibilities in treating hyperlipidemia]

CSÁSZÁR Albert

[In the fight against atherosclerosis, statin therapy is one of the most important elements. On the basis of data from the past few years the clinical introduction of a more effective statin is not expected, however, in order to improve cardiovascular prevention further development of agents that reduce LDL-cholesterol levels more effectively than currently used statins is warranted. The need for the development of new cholesterol-lowering therapeutic options is also supported by the existence of statin intolerance. The currently available combination therapies do not provide additional mortality benefits compared with statin monotherapy. The new solutions include fourth-generation statin molecules that primarily aim to enhance the NO-donor capacity of statins, and to reduce their muscle toxicity. Certain compounds that affect cholesterol synthesis (squalene synthase inhibitors, MTP inhibitors, ACAT inhibitors) need to be further analysed because of the risk of side effects. The use of an antisense oligonucleotid that blocks the mRNA of apoB, the main protein on the LDL-particle and antibodies that inhibit the protein PCSK9 that promotes the intracellular breakdown of the LDL-receptor seems to be much more promising. Besides the lowering of LDLcholesterol level, studies have focused on the benefits of increasing HDL-cholesterol levels. Unfortunately, recently completed analyses show that new forms of the strong HDL-C increasing nicotinic acid have not provided any additional benefit when added to statin therapy. Similarly, the adverse effects associated with the promising CETP inhibitors and the lack of additional benefit when combined with statins question the significance of this drug class. The necessity for an absolute increase of HDL-cholesterol levels needs to be revised on the basis of new data, in other words, the exact role of the HDL particle in atherosclerosis needs to be further investigated.]

Lege Artis Medicinae

[The aims and latest results of clinical toxicological analysis]

RÓNA Kálmán

[Almost 80 percent of poison-related deaths are caused by drugs. The overwhelming majority of today's clinical toxicological work is comprised of cases of toxic level drug overdose, drug mixups, adverse effects during therapeutic drug administration, as well as intoxication from drug abuse. A prerequisite of adequate therapy of intoxication is the qualitative and quantitative determination of the compounds causing it. The two elements of systematic toxicological analysis are the screening test and the confirmatory test. The review touches on the toxicologic use of the hyphenated chromatographic-spectroscopic instruments and on the alternative biological matrices. It is known that the effects and toxic side-effects of many drugs show substantial interindividual differences even in the same doses. One of the possible causes of this phenomenon is a genetically determined polymorphic drug metabolism. Some pharmacogenetically determined anomalies in drug administration, particularly enzyme inhibition and induction, are of clinical toxicological importance.]

Clinical Oncology

[Biopharmaceuticals]

LÉVAY György

[Biopharmaceuticals represent a new class of very effective medications in the management of debilitating and often life-threatening diseases but the costs of these therapies exceed the costs of regular therapies. Biological medicinal products (i.e. smaller proteins or monoclonal antibodies) are mostly complex macromolecules, produced by microbial or mammalian cell cultures in bioreactors through application of complex process technologies. After patent expiry, the production of compounds with comparable quality features and comparable clinical safety and effi cacy profi les become available, however, the complexity of the macromolecules means they are not equivalent in the sense of small molecule generics. Biologics that are similar to a given licensed reference compound and meet regulatory requirements within this context can be termed as biosimilars. The similarity of the two products must be appropriately proven during the products’ marketing-authorisation procedure. As more and more biosimilar compounds have been approved by regulatory authorities in the EU and US it is expected that these products will bring signifi cant healthcare savings and much greater patient access to these revolutionary therapeutics.]

Lege Artis Medicinae

[TREATMENT APPROACHES OF CHRONIC HEPATITIS B IN HUNGARY]

TORNAI István, NEMESÁNSZKY Elemér

[Today, there are less patients with active chronic hepatitis B requiring treatment than patients with chronic hepatitis C. However, the course and outcome of chronic hepatitis B is usually more severe, therefore, the disease has not lost importance. The most dangerous risks are the development of liver cirrhosis and hepatocellular carcinoma. The disease may present in various forms. Symptom-free carriers only need follow-up and hepatologic care. In the active stages with elevated liver enzymes and high level of viral nucleic acid (either HBeAg negative or positive), however, antiviral treatment is strongly indicated. There are two main forms of treatment. Alfa-interferon-based therapy, which is applied for a defined period of time, has a direct antiviral and immunomodulatory effect, but has several adverse effects. Long-term nucleoside analogue treatment represent the other treatment modality. These drugs are administered orally, have minimal side effects, but after some time resistant mutants may develop. Traditional interferon has recently been replaced by pegylated interferon alfa-2a with much better pharmacokinetic properties. Lamivudine has been in use for the longest time of the nucleoside analogues. Its efficacy is high, but after 3 to 4 years of treatment, resistant mutants appear in about 70% of cases. Of the most recent compounds, adefovir dipivoxil has recently become available in Hungary; it is primarily recommended in cases with lamivudine resistant mutants. There are promising new drugs in the stages of clinical trial; of these, entecavir has already been approved in the United States.]

LAM KID

[Potential antiosteoporotic agents from plants]

BALLA Bernadett