Lege Artis Medicinae

OCTOBER 01, 2000

[Molecular mechanisms of cardiac hypertrophy and heart failure]

MIKALA Gábor, PETŐ Mónika, VÁLYI Nagy István, CSÁSZÁR Albert

[In this review, the most important molecular mechanisms leading to cardiac muscle hypertrophy and consequentially to heart failure are detailed. In numerous instances, understanding molecular mechanisms offers the possibility for pharmacotherapeutic intervention. First, trimeric G-proteins and their attached intracellular signaling pathways are introduced, with special emphasis on the pathways elucidated by transgenic animal models. In this area, there are several clinically effective drugs to influence cardiac hypertrophy, including ACE inhibitors, angiotensin receptor antagonists, as well as a- and B-adrenergic receptor blockers. Mitogen activated protein kinases participate later in the hypertrophic cascade. There are ongoing investigations on the potential therapeutic use of lipid-soluble statins these are indirect inhibitors of Ras-farnesylation. Altered cellular Ca2+-homeostasis is fundamental with respect to cardiac muscle hypertrophy and heart failure. The third part of this article investigates the role of the calcium/calmodulin dependent protein phosphatase called calcineurin in these processes. Administration of cyclosporin A or tacrolimus (both are inhibitors of calcineurin) may not be recommended in most forms of cardiac hypertrophy, however, in certain settings they may prove to be valuable therapeutic agents. One of the most serious, not yet properly addressed problem of late stage heart failure is the development of ventricular arrhythmias caused by repolarization abnormalities. Certain mechanisms of this phenomenon are highlighted with a special note on Nat-Cat exchange inhibitors as one of future therapeutic agents of much promise. ]

Lege Artis Medicinae

JUNE 01, 2000

[Practical aspects of screening for microalbuminuria in diabetic patients]


[INTRODUCTION - The importance of measuring microalbuminuria is well established, however, controversy still exists regarding the type of urine specimen to be used for detecting early renal impairment of diabetic patients. PATIENTS AND METHODS – To evaluate practical aspects, albumin concentration and albumin to creatinine ratio of first void urine samples as well as urinary albumin excretion in timed specimens were determined by immunoturbidimetric method 3 times within 3 weeks in 192 adult diabetic patients (136 men, 56 women; type 1/type 2: 90/102; age: 51.4=10.8 years; duration of diabetes: 15.3+9.1 years; body mass index: 27.9+4.6 kg/m2; HbA1c: 8.5+1.5 %; actual blood pressure: 13814/82+8 mmHg; serum creatinine: 94+20 umol/l; x+SD). RESULTS - According to the urinary albumin excretion values, one third of patients (31.2%-30.7%-34.4%) were normoalbuminuric (<30 mg/24 hours), more than half of the patients (55.8%-57.3%-53.6%) proved to be microalbuminuric (30-300 mg/24 hours), while the remaining group of patients (13.0%-12.0%–12.0%) was macroalbuminuric (>300 mg/24 hours). Comparing the results of successive measurements good correlation was found between the same laboratory values (urinary albumin excretion: K=0.64; K=0.67; urinary albumin concentration: K=0.60; K=0.62; albumin to creatinine ratio: K=0.54; K=0.61; first vs. second and second vs. third measurements, respectively). The percentage of patients being in the same range of albuminuria (i.e. normo-, micro-or macroalbuminuria) at successive measurements was 79.7-81.2% with urinary albumin excretion values, 77.1-77.6% with urinary albumin concentration and 74.5-78.6% with albumin to creatinine ratio. Good correlations were found between urinary albumin excretion and urinary albumin concentration (K=0.54; 0.54; 0.57) and nearly the same correlations were observed between urinary albumin excretion and albumin to creatinine ratio (K=0.49; 0.47;0.54) at different series. Using values of urinary albumin excretion for comparison at all measurements, 79.3% sensitivity and 69.5% specifity were found for urinary albumin concentration whereas 74.6% sensitivity and 68.8% specifity were documented for albumin to creatinine ratio. CONCLUSION - Beside the standard measurement of urinary albumin excretion in timed urine samples, the use of the more convenient morning urinary spot collection could also provide useful results (urinary albumin concentration or albumin to creatinine ratio) for detecting early renal involvement in diabetic patients. ]

Lege Artis Medicinae

JUNE 01, 2000

[Cardiovascular risk management ]


[Recent success in the management of cardio vascular disease does not render prevention unimportant, rather emphasizes its importance. The process of prevention begins with setting the priorities, followed by determination of the risk of the patient based on clinical data. Life style, laboratory results and signs of subclinical atherosclerosis have great impact on the combined multifactorial risk. Professional advice to lifestyle modification can significantly reduce the risk. Additionally, adequate treatment of hypertension, diabetes mellitus and cholesterol abnormalities serve as preventive procedures, as well as the necessary coronary intervention and revascularization. Longer life expectancy, as the result of prevention, has both social and financial benefit. This result can only be expected after the required investment. ]

Lege Artis Medicinae

MAY 01, 2000

[The role of apoptosis in human diseases]


[Apoptosis and mitosis control the homeostasis of various cell populations. Several diseases are characterised by too much or to small amount of apoptosis. Carcinogenesis itself is connected with a decrease in apoptotic activity and malignant neoplasms are also known to show low apoptotic index. However, each type of malignant tumors should be viewed as a distinct entity, regarding the capacity for the induction of apoptosis especially. The role of apoptosis in the pathogenesis and progression of autoimmune, infectious, neurodegenerative diseases and alterations in the liver, kidney, lung and heart is also discussed, with special emphasis on therapeutic possibilities influencing the imbalance of apoptosis. ]

Lege Artis Medicinae

FEBRUARY 01, 2000

[Standardizing the results of Diabcare Hungary; A method for comparison and quality Improvement]

TABÁK Gy. Ádám, TAMÁS Gyula, KERÉNYI Zsuzsa

[INTRODUCTION – DiabCare, the monitoring system of the WHO/IDF-Euro was developed for continuous quality improvement of diabetes care based on a structured and standardized diabetes dataset. PATIENTS AND METHODS - Data from 5 DiabCare Hungary centers with different patient populations were adjusted for demographic parameters and compared to the 2403 records of the national dataset collected between 1995–97. RESULTS - More than half of the investigated patients were >56 years old (centers analyzed in detail: 20–83%), one third of them had an age 36-55 years (17-52%), 45% were male (27-63%). The prevalence of type 1 DM was 29% (0–80%). Almost one third of the patients had a diabetes duration >15 years (14-58%). Eyes were examined in 79% (28-98%), retinopathy was found in 29% (28–81%, minimal change after standardization). Risk factor identification was above 80% in all centers (except in center 3: 16-94%). Rate of patients with risk factors: HbAlc >8%: 43%; triglycerides >2mmol/l: 33% (in center 5 lower, 17%; after standardization 37%), blood pressure (>160/95 Hgmm), smoking and alcohol consumption together 15%. Albuminuria was examined in 55% (25–89%), with microalbuminuria present in 24% (0-38%). The frequency of self-monitoring and of severe hypoglycemia (49 and 5%) paralleled the relative weight of type1 DM patients during standardization. CONCLUSION - It is concluded that centralized evaluation and anonymous comparison of crude and adjusted data might be helpful in assessing and improving the quality of diabetes care. ]

Clinical Neuroscience

JULY 30, 2021

[Personalised epilepsy treatment]


[Epilepsy is one of the most common chronic neurological disease in childhood. Patients with epilepsy – even with so-called benign epilepsy – need medication for years. During this time, children go through a very big change, not only gaining weight and height, but also changing hormonal and metabolic processes. Maturation processes in different brain areas also take place at different rates depending on age. All of these should be considered when preparing a therapeutic plan. In everyday practice after the diagnosis of epilepsy, the applied drug is most often selected based on the shape and type of seizure. However, a number of other factors need to be considered when designing a therapeutic strategy: 1. efficacy (form of epilepsy, type of seizure), 2. age, gender, 3. pharmacological properties of the drug, 4. adverse drug reaction profile, 5. lifestyle (community), figure (skinny, corpulent, obese), 6. other comorbidities (nutrition, behavioral and learning problems, circulatory disorders, kidney or liver disease), 7. expected interactions with other drugs already used, 8. genetics, 9. other aspects (drug registration and prescription rules). The purpose of this article is to help to decide which antiepileptic drugs are expected to have the least side effects in a particular child with different comorbidities and which medications should be avoided if possible.]