Lege Artis Medicinae

[THE CLINICAL PHARMACOLOGIC BASIS OF THE SAFE USE OF STATIN ANALOGS]

KERPEL-FRONIUS Sándor

JUNE 20, 2005

Lege Artis Medicinae - 2005;15(06)

[Statins, specific inhibitors of the 3-hydroxy-3-methylglutaryl- coenzyme A (HMG-CoA), decrease significantly pathologically elevated cholesterol levels. The effectiveness and the side effects of the different analogs depend on their inhibitory potency, lipid solubility, active uptake into the liver cells and on the difference in their metabolism. The statins can be divided into three groups on the basis of their clinical effectiveness: the highly effective agents are rosuvastatin and atorvastatin; simvastatin exhibits an intermediate activity, while lovastatin, pravastatin and fluvastatin are the least active drugs. The main metabolic pathways of the statins are oxidation and glucoronidation and finally the spontaneous inactivation by lactone ring formation of the glucoronidated products. Gemfibrozil increases the plasma level of all statin analogs by inhibiting the activity of UGT1A1 and UGT1A3 isoenzymes of the UDPglucoronosyltransferase. Therefore, when a statinfibrate combination is needed, fenofibrate and bezafibrate are recommended, the metabolism of which are linked to other UGT isoenzymes. Similarly elevated plasma levels are produced by inhibiting the specific cytochrome isoforms participating in the oxidation of a particular statin. Severe side effects are rarely observed. The most frequent adverse reaction is the development of myopathy of various severity. Using various statins rhabdomyolysis occurred in 0.0-0.3 cases /100 000 statin prescriptions if the already withdrawn cerivastatin is not considered. The statin+gemfibrozil combination increases the number of rhabdomyolysis approximately tenfold. The long-term benefit of statin therapy far exceeds the risk of the treatment. For achieving very low lipid target values even the most effective statins must be used in high doses. Nevertheless, this goal cannot be reached in about 20% of the cases. High dose statin treatment should be administered with the gradual increase of the dose, tight control of the patients and by meticulously selecting the drugs given simultaneously. Further development can be expected from the application of agents with new mechanisms of action, such as the cholesterol uptake inhibitor ezetimibe.]

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Lege Artis Medicinae

[SUBCONJUNCTIVAL NEMATODE INFECTION]

ACZÉL Klára, DEÁK György, FARKAS Róbert, MAJOROS Gábor

[INTRODUCTION - Nematode infection of the eye occur only sporadically in the continental area. The pathogenic parasite in these cases is usually a Dirofilaria species, mostly D. repens. CASE REPORT - A case of human subconjunctival dirofilariosis is reported, where acquisition from abroad or animal contact in the background of the infection were excluded. The surgical removal of the entire living worm resulted in the complete cure of the patient. CONCLUSION - Knowing the occurrence of Dirofilaria infection of dogs and the increasing spread of the vector mosquitoes during the summer (in towns, too), the increasing occurrence of human dirofilariosis affecting the eye and orbital area in 10-20% of the cases must be taken into account.]

Lege Artis Medicinae

[THE PLACE OF OPEN SURGICAL INTERVENTIONS IN THE ERA OF LAPAROSCOPIC HIATAL HERNIA RECONSTRUCTION AND ANTIREFLUX SURGERY]

ALTORJAY Áron, VARGA István, SÁRKÁNY Ágnes, TÓTH Sándor, MUCS Mihály, HAMVAS Balázs, PAÁL Balázs, THAN Zoltán

[INTRODUCTION - The leading role of laparoscopy in the surgical treatment of functional diseases of the gastro-esophageal junction has become indisputable. But has the time of the “classic”, open surgical interventions really gone for good? PATIENTS AND METHODS - Between January 1., 2000 and December 31., 2004 we performed hiatal reconstruction and antireflux plastics for 186 patients. 83.3% (155/186) of the operations was performed laparoscopically, while 16.7% (31/186) with the traditional approach. The average age of patients was 46.9 years, 7% of the operations was performed on children. In case of recurrent paraoesophageal hernias the surgical plan was drawn up based on the result of the barium swallow X-ray performed after endoscopic clipping of the Z-line. In case of a brachy-esophagus, we formed the neo-esophagus by performing the Collis-Nissen operation modified by us (Neodinium magnet + plastic sliding scale) from the traditional abdominal exposure. RESULTS - The indication for hiatal reconstruction and antireflux operation was sliding hernia in 68.2%, paraesophageal hernia in 17.8% and reflux disease in 14%. We observed signs of panmural esophagitis in 22%, while latent or true brachy-esophagus in 10.7%. Antireflux procedures were grouped as Nissen type operation in 82.7%, Toupet type in 9.67%, Narbona in 2.1%, Belsey-Mark IV in 1.61%, and resection type operation in 3.76%. To narrow the diaphragmatic openings, two sutures were needed in most cases (57.1%). Conversion to laparotomy was necessary in 3.2%. We observed recurrences in 3.3% after laparoscopic interventions. In case of open operations we experienced no recurrences in the studied period. The barium swallow X-ray examination performed after endoscopic clipping of the Z-line could reveal brachy-esophagus before the operation. CONCLUSION - Open surgical interventions can not fall into oblivion even in the age of laparoscopic hiatal reconstructions and antireflux plastics. Open surgical procedures are justified even in the new milennium in cases when the patient's medical history contains upper abdominal operations - due to an increased risk of injury because of adhesions -,in cases of primarily recurrent paraesophageal hernias after an unsuccessful open and/or laparoscopic reconstruction, as well as in cases of reflux with complications.]

Lege Artis Medicinae

[Late effects on renal glomerular and tubular function in childhood cancer survivors]

BÁRDI Edit, OLÁH V. Anna, BARTYIK Katalin, ENDREFFY Emőke, JENEI Csaba, KAPPELMAYER János, KISS Csongor

Lege Artis Medicinae

[Life’s deep-frozen libraries - Stone’s throw from the new generation of biobanks]

PÓS Zoltán

Lege Artis Medicinae

[Poliomyelitis - Success and problems in eradication]

BUDAI József

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ÇAKAR Emel Nafiye, GÖR Zeynep, YEŞIL Gözde

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal inherited metabolic disorder in which the β-oxidation of the long chain fatty acids is defective. The clinical presentation may be in various forms; it presents itself in the severe form during neonatal and infantile periods and as the less severe myopathic form in the school age and adolescence. While the severity of the rhabdomyolysis attacks varies, occasionally the clinical course may be complicated with acute renal failure. Acylcarnitine analysis may help in the diagnosis of CPT II, but its normality does not indicate the absence of the disease. If there is strong suspicion, genetic analysis should be performed on the cases. In this article, we present a 15-year-old male patient who had two rhabdomyolysis attacks triggered by infection and starvation. Acylcarnitine analysis of the case was normal, CPT II deficiency was considered when the history was evaluated, and CPT II gene c.137A>G (p.Gln46Arg) homozygous novel pathogenic mutation was detected. CPT II deficiency is one of the most common causes of metabolic rhabdomyolysis in patients with recurrent episodes of rhabdomyolysis.

Lege Artis Medicinae

[Lipid lowering therapy during COVID-19 pandemic]

MÁRK László

[The COVID-19 pandemic posed significant challenges to all healthcare systems of the world as created a new situations above the large number of people infected, solutions of which were lacking any previous patterns. Former experiences were specifically needed among physicians who practised usually with therapies supported by evidence based clinical experiences thus they were working along the principles of Evidence-Based Medicine. The new observations and recommendations for treating infected patients increased gradually, however they were not always well-founded by the general urgency. In this situation, physicians faced often problems of the patient’s former medications since they had to focus on the therapy of the prevalent life-threatening condition. In such cases, therapy as lipid lowering, which is inherently inimically and lightly taken, may be omitted even more often. Basic drugs of lipid lowering are statins. They are used to reduce cholesterol levels and the risk of cardiovascular events, but they have also been described as having beneficial effect on the new viral infection. In this effect, the statins beyond the well-known anti-inflammatory impact and increasing the expression of angiotensin-converting enzyme-2 further mechanisms can take part as well. These may include among others the promoted breakdown of lipid rafts, which directly inhibits the entry of coronavirus into the cell through the S protein by decreasing the level of cholesterol required for this proceeding. In a group of more than 1200 statin treated and SARS-COV-2 infected patients the overall mortality rate by the 28th day was 48% lower than among the non-statin-users. According to a meta-analysis of nearly nine thousand COVID-19-infected statin users, they had 30% lower mortality rate or serious complications. Up to date observational studies suggest that statin therapy and the administration of other lipid lowering drugs should be continued or initiated according to the guidelines also during the COVID-19 infection.]

Lege Artis Medicinae

[Notes on the management of hypertension in chronic kidney disease ]

AMBRUS Csaba

[The prevalence of hypertension among pa­tients with chronic kidney disease is high, reaching more than 80%. Hypertension is both one of the main causes and also the most common consequence of chronic kidney disease. It is also a main factor responsible for the high cardiovascular morbidity and mortality in this patient population. Blood pressure control can improve patient outcomes, lower cardiovascular risk and slow down the progression of kidney dis­ease, irrespective of the underlying cause. The optimal therapy should therefore focus not only on blood pressure reduction but also on renoprotection. Basic understanding of the renal pathophysiology in hypertension and renal effects of various medications is of paramount importance. In this review, we summarized cornerstones of the antihypertensive therapy in patients with chronic kidney disease. The management of patients receiving kidney replacement therapies, such as hemodialysis, peritoneal dialysis or transplanta­tion requires special knowledge and expe­rience, therefore it is not discussed here. The aim of this review was to allow non-nephrologist physicians to take care of their kidney patients with more confidence and effectiveness.]

Hypertension and nephrology

[Evaluation of arterial stiffness in children. Guidelines for the practice]

CSEPREKÁL Orsolya, KIS Éva, SZABÓ J. Attila, REUSZ György

[Assessment of early atherosclerosis and decreased arterial elasticity to recognise the cardiovascular dysfunction in high-risk patients has gained importance in the past decade. Since 1990, more than 630 papers have been published in the adult and pediatric literature. Methods of early risk assessment in adults are well determined in international recommendations. The aim of the present work is to review the suggestions of the American Heart Association helping us to find the most appropriate method for the non invasive methods of cardiovascular assessment of young adults and children. Furthermore, multicentric studies should be conducted to create a Framingham like score system for pediatric patients, to render cardiovascular risk assessment much easier for the every day routine.]

Lege Artis Medicinae

[Chlamydia pneumoniae in coronary arteries of young adults]

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[INTRODUCTION - An association of Chlamydia pneumoniae (C. pneumoniae) with coronary heart disease has been found with seroepidemiological methods. This organism was demonstrated in atheromatous plaques by electron microscopy, immunohistochemistry, and polymerase chain reaction. MATERIAL AND METHODS - To better understand the significance of the presence of C. pneumoniae in atheromatous plaques, we examined coronary artery segments from young adults (15-34 years) with and without atherosclerosis. 74 samples of left anterior descending artery were examined immunohistochemically for the presence of C. pneumoniae by the monoclonal antibody RR402. RESULTS - C. pneumoniae was identified in the atheroma in 11 of 17 cases (65%) and in preatheroma in 6 of 15 cases (40%), in fatty streak in 7 of 23 cases (30%) and in intimal thickening in 1 of 14 cases (7%). C. pneumoniae was not found in the intimal and medial layer of the normal-appearing coronary arteries. C. pneumoniae was detected in the adventitia in 51 cases (67%) of the coronary arteries: in the normal arteries and initial lesions in 27 of 42 cases (63%), and in the advanced lesions in 24 of 32 cases (75%). Correlation was observed between the C. pneumoniae positive cases and cigarette smoking. CONCLUSION - Our results suggest that C. pneumoniae may relate to the severity of atherosclerosis in the youth, thus may initiate atherosclerotic injury or facilitate its progression along with other risk factors.]