Lege Artis Medicinae

[ALTERATIONS IN MYOCARDIAL CONTRACTILE PROTEIN COMPOSITION IN DIASTOLIC HEART FAILURE]

PAPP Zoltán, BORBÉLY Attila, ÉDES István

JULY 14, 2007

Lege Artis Medicinae - 2007;17(06-07)

[Disturbances in ventricular relaxation may lead to the development of diastolic heart failure. The analysis of left ventricular endomyocardial biopsy specimens may help understand the underlying structural and functional changes. Such analyses have lead to the recognition that at the optimal sarcomere length of the Frank- Starling mechanism (i.e., at 2.2 μm), passive force values of the cardiomyocytes are significantly higher in individuals with diastolic heart failure than in healthy controls. As a probable explanation to this finding, increased expression of the stiffer N2B isoform of the myofilamental titin protein, at the expense of the more elastic N2BA titin isoform, has been recognized. Moreover, decreased phosphorylation of the contractile proteins was also suggested to contribute to the development of diastolic heart failure. These changes together, and along with an increase in extracellular collagen content, may greatly contribute to the relaxation disturbance observed in diastolic heart failure.]

COMMENTS

0 comments

Further articles in this publication

Lege Artis Medicinae

[Clinical consensus conference on COPD]

TAMÁSI Lilla

Lege Artis Medicinae

[THE USE OF BETA RECEPTOR BLOCKERS IN CHRONIC HEART FAILURE]

CZURIGA István

[The beneficial effects of treatment with betablockers in patients with chronic heart failure have been demonstrated in several large, prospective, randomised, placebo-controlled clinical trials. In large trials with mortality as the endpoint, the long-term use of bisoprolol, carvedilol, nevibolol and metoprolol succinate have been associated with a reduction in total mortality, cardiovascular mortality, sudden cardiac death and death due to progression of heart failure in patients of functional classes II-IV. These favorable clinical experiences warrant a recommendation that beta-blockers should be used in all haemodynamically stable heart failure patients with reduced left ventricular systolic function who are on standard treatment, unless contraindicated. In this review, the most important data of clinical trials and practical considerations of therapy with beta-blockers in heart failure are summarized.]

Lege Artis Medicinae

[THE USE OF DIRECT VASODILATORS AND DIGITALIS IN CHRONIC HEART FAILURE]

DÉKÁNY Miklós

[For the optimal treatment of heart failure patients with systolic dysfunction, supplementation of the standard diuretics plus neurohormonal antagonists treatment with the direct vasodilator combination dihydralazine+nitrate, as well as with digitalis may be necessary. Addition of hydralazine/dihydralazine+nitrate to the treatment of chronic heart failure is recommended if ACE-inhibitors or angiotensin-receptor blockers cannot be administered. Beta blockers should also be used in these cases. If symptoms persist or worsen, addition of this combination to the standard therapy is reasonable. Supplementation with digitalis, mostly digoxin should be considered in similar conditions. It can be especially beneficial for patients with high-ventricular-rate atrial fibrillation. To achieve maximal survival benefit, the dose of digoxin must not exceed 0.125 mg/day. Low body weight or muscle mass, significantly reduced renal function may make further dose reduction necessary. If renal function is severely limited, digitoxin instead of digoxin may be used.]

Lege Artis Medicinae

[Addictions in the focus - Readers’ questions answered by dr. János Szemelyácz]

SZEMELYÁCZ János

Lege Artis Medicinae

[RECOGNITION AND MANAGEMENT OF ACUTE HEART FAILURE]

KARLÓCAI Kristóf

[Acute heart failure may develop in previously healthy hearts. Nevertheless, structural abnormalities can facilitate its development and also, chronic heart failure can progress into acute stage. Considering the total cost of care in the patient's life, this is the most expensive heart disease. The clinical signs and physical abnormalities are usually of diagnostic power, however, instrumental investigations are necessary to recognize complications and to guide therapy. Patients should be monitored in well equipped coronary care units. Therapy consists of medications, coronary revascularization and use of mechanical assist devices.]

All articles in the issue

Related contents

Clinical Oncology

[Diagnosis and therapy of childhood brain tumors – an update]

GARAMI Miklós

[Childhood cancers are rare disorders. The average annual age-standardized incidence is 149/1000000 (0-14 yrs). Diagnosis of childhood brain tumors, despite the specifi c localization and advanced imaging techniques can cause diffi culties. In recent years, due to better early recognition, number of surgically removable brain tumors is increasing. Early detection of the disease (clinical knowledge), use of modern imaging (fMRI) techniques and detection of characteristic molecular lesions allow up-to-date diagnosis and successful treatments. These approaches provide the basis for risk-adapted personalized treatment options]

Clinical Oncology

[The use of NGS in oncology in diagnostic setting]

BECSÁGH Péter

[Today the information could be the basis of further development by collecting, saving, structuring and analyzing them. Inside the living organism and inside viruses the biochemical storage system was evolved. The linear coding inside macromolecular structures could create and store a series of building block combinations along the chain structure. Those chemical structures are the so called information coding macromolecules, for example, the polypeptides and nucleic acids. Analysis of the genetically coded functionalities of tumor cells has a great impact in the oncological setting. The connected functions of inherited or acquired alterations inside the tumor cell clones are the main contributors of tumor evolution and surviving, although provide a way to target possible mechanism and touch points. Today the oncodiagnostic use of next generation sequencing technology focus on tumor evolution and tumor surviving connected gene set analysis. This kind of gene panel analysis connected to NGS technology is enough enforced - enforced enough - to reach the diagnostic level, but one still need to take care about the quality and standardization to meet the IVD conditions.]

Lege Artis Medicinae

[MOLECULAR DIAGNOSTICS OF EPIDERMAL GROWTH FACTOR RECEPTOR IN NON-SMALL CELL LUNG CANCER]

TÍMÁR József, OSTOROS Gyula

[One of the most useful markers of non-small cell lung cancer is epidermal growth factor receptor (EGFR) protein expression. Recently it was found that the EGFR gene may be amplified or mutated in non-small cell lung cancer rendering this gene product an ideal target for therapy. The introduction of molecularly targeted therapy into the clinical practice represents a milestone in the management of non-small cell lung cancer. However, our knowledge on the prognostic and predictive factors that will define the efficiency of anti-EGFR therapy is limited. In clinical practice, some common patient and disease features (e. g., smoking habit, gender, histological type) are still more dependable predictors than the fine molecular properties that may directly affect therapeutic response. The indication of anti-EGFR therapy in Hungary is based on the immunohistochemical detection of the EGFR protein, therefore, it is important that these tests are performed as reliably as possible. On the other hand, mutations in the EGFR gene may render the tumour resistant or, in contrary, especially sensitive to EGFR inhibitor therapy. The sequence of the diagnostic steps to define the genotype and phenotype of non-small cell lung cancer has a great importance in terms of cost-efficiency of the therapy.]

Clinical Oncology

[Molecular profi les in therapeutic strategy]

PETÁK István, SCHWAB Richárd

[In 2013, 10 years after the completion of the human genome, the cancer genome project has identifi ed almost all possible cancer genes, which could be responsible for the malignant transformation and progression. These genes are called „driver” genes, and the pathogenic mutations to be „driver” mutations. The census of „driver genes” in 2013 counted 138 genes and 1.5 million mutations. The situation is further complicated by the fact that up to 8 „driver” gene can be activated simultaneously in the same tumor, furthermore, the profi le may change during tumor growth and metastatization. 2013 was a turning point also because several targeted therapies were registered. Currently there are about 30 targeted drugs in clinical use and more than 200 targeted compounds in clinical development. This means that in 3-4 years the number of drugs will at least double. Most of the current patients can only access these compounds in clinical trials. But, patient already benefi t signifi cantly more even from phase I clinical trials, if they are selected based on the molecular profi le of the tumor. Fortunately, the advancements of next generation sequencing technologies provide the opportunity to identify all „driver” genes, - the whole molecular profi le, - in the patient’s tumor for the cost of one month targeted therapy. But the information generated can be only used in clinical practice if the results are processed by „molecular info-bionics”.]