Lege Artis Medicinae

[Reference price system as a potential method for pharmaceutical cost containment]

KALÓ Zoltán, VINCZE Zoltán, LOVAS Kornélia, BODROGI József

SEPTEMBER 20, 2002

Lege Artis Medicinae - 2002;12(09)

[Reference pricing is one of the potential cost containment methods for pharmaceuticals. Authors describe its main types and the international examples of reference pricing together with technical details of its introduction. Consequences of the system are grouped into 5 categories: pharmaceutical expenditure, other health care expenditure, medical implications, consequences on patients and their health status, and political effects. They propose that reference pricing should be introduced only gradually based upon recommendations by multiprofessional teams. The system should be evidence based which includes clinical effectiveness, safety, compliance and cost-effectiveness. ”Real” active substance based reference pricing is justifiable for broad ranges of pharmaceuticals. General introduction of therapeutic reference pricing in Hungary, however, may result in serious negative consequences.]



Further articles in this publication

Lege Artis Medicinae

[The effect of angiotensin receptor antagonists in diabetic nephropathy]

BÍBOK György

[Influencing the renin-angiotensin system through receptor blockade has become a new therapeutic approach toward the treatment of several morbidities, i.e. hypertension, cardiac failure and diabetic nephropathy. The current paper reviews the importance of diabetic nephropathy, the physiology of the renin-angiotensin system and specific effects of receptor blockade on different organs based on 3 new studies (published last year) using angiotensin-II receptor blockers. The paper gives a summary of the IRMA, IDNT and RENAAL studies, including their clinical and therapeutic significance in general practice as well as in specialized diabetes care. The new therapeutic approach (with an excellent safety profile, and infrequent side effects) could delay the progression or might even prevent the manifestation of diabetic nephropathy not only with lowering blood pressure but with its direct effects on target tissues as well. The angiotensin-II receptor blocking agents might be useful for the treatment of cardiac failure in hypertensive patients.]

Lege Artis Medicinae

[Drug treatment possibilities in chronic liver diseases]

HAGYMÁSI Krisztina, LENGYEL Gabriella, FEHÉR János

[Alcoholic and drug induced liver diseases, nonalcoholic steatohepatitis, hepatitis C and B chronic hepatitis, autoimmune diseases (primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis) and metabolic disorders (hemochromatosis, Wilson's disease) are the main chronic liver diseases. Authors summarize, based on the latest literature data, the medications of chronic liver diseases, emphasizing the treatment of the everyday practice. Natural and synthetic antioxidants are approved for the treatment of chronic alcoholic liver diseases besides abstinence, with diet of adequate quality and quantity. Nucleoside analogues (lamivudin) are recommended for the first-line therapy of the treatment of chronic hepatitis B. Interferon is presently considered the optimal treatment for only certain patients. Interferon and ribavirin combined therapy is well-established in the treatment of chronic hepatitis C. Ursodeoxycholic acid is the beneficial treatment option for primary biliary cirrhosis and primary sclerosing cholangitis. Prednisolon and azathioprine constitute the basic therapy of autoimmune hepatitis. Presumably, in the future, new strategies based on immunosuppressive combinations will play a crucial role. The chelating deferoxamine has less important part in the treatment of hemochromatosis. D-penicillamine still plays principle role in the medication of Wilson's disease.]

Lege Artis Medicinae

[QT dispersion - the surface ECG marker of arrhythmic risk]

KUN Csaba, CZURIGA István, LŐRINCZ István

[During the past decade numerous publications have reported the pathophysiological and clinical value of QT dispersion. Increased QT dispersion was observed to be associated with proarrhythmic drug effects, prediction of mortality in heart failure and risk assessment after acute myocardial infarction. Based on the results of the repolarization process research and other significant clinical studies, the meaning and the usefulness of QT dispersion seems to be challenged. The original concept of portraying QT dispersion as a direct measure of regional heterogeneity of myocardial refractoriness is seriously flawed. At the same time, disproving this concept is not a good reason for stating that QT dispersion does not exist. The measurement of QT dispersion seems to be an approximate expression of repolarization abnormalities and should not be taken as a gold standard for a noninvasive estimate of repolarization abnormalities. However, we presently have no decent and widely available alternative to address repolarization abnormalities in standard 12-lead ECG. The authors present the pathophysiological meaning of QT dispersion, the controversies of automatic and manual methodology and the possible clinical relevances based on the most recent studies.]

Lege Artis Medicinae

[Cytological and genetic background of senescence]


Lege Artis Medicinae

[Oral clodronate for the prevention and therapy of bone metastasis of breast cancer]


[1600 mg/d oral clodronate has been shown to reduce the incidence of skeletal complications significantly in advanced breast cancer cases with lytic bone metastases. Analysis of clinical trials revealed that the adjuvant, prophylactic administration of clodronate possibly decreases the number of non-skeletal metastases and might prolong survival.]

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Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

Evaluation of the effectiveness of transforaminal epidural steroid injection in far lateral lumbar disc herniations

EVRAN Sevket, KATAR Salim

Far lateral lumbar disc herniations (FLDH) consist approximately 0.7-12% of all lumbar disc herniations. Compared to the more common central and paramedian lumbar disc herniations, they cause more severe and persistent radicular pain due to direct compression of the nerve root and dorsal root ganglion. In patients who do not respond to conservative treatments such as medical treatment and physical therapy, and have not developed neurological deficits, it is difficult to decide on surgical treatment because of the nerve root damage and spinal instability risk due to disruption of facet joint integrity. In this study, we aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) on the improvement of both pain control and functional capacity in patients with FLDH. A total of 37 patients who had radicular pain caused by far lateral disc herniation which is visible in their lumbar magnetic resonance imaging (MRI) scan, had no neurological deficit and did not respond to conservative treatment, were included the study. TFESI was applied to patients by preganglionic approach. Pre-treatment Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores of the patients were compared with the 3rd week, 3rd month and 6th month scores after the procedure. The mean initial VAS score was 8.63 ± 0.55, while it was 3.84 ± 1.66, 5.09 ± 0.85, 4.56 ± 1.66 at the 3rd week, 3rd month and 6th month controls, respectively. This decrease in the VAS score was found statistically significant (p = 0.001). ODI score with baseline mean value of 52.38 ± 6.84 was found to be 18.56 ± 4.95 at the 3rd week, 37.41 ± 14.1 at the 3rd month and 34.88 ± 14.33 at the 6th month. This downtrend of pa­tient’s ODI scores was found statistically significant (p = 0.001). This study has demonstrated that TFESI is an effective method for gaining increased functional capacity and pain control in the treatment of patients who are not suitable for surgical treatment with radicular complaints due to far lateral lumbar disc hernia.

Lege Artis Medicinae

[Risk of nonsteroidal antiinflammatory drugs. Focus on aceclofenac]


[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals. Nevertheless, a number of studies emphasized that NSAIDs were damaging not only the gastrointestinal (GI), but also the cardiovascular (CV) system, could increase the blood pressure, the frequency of coronary events (angina, myocardial infarction) and stroke incidence, as well as they might deterio­rate renal functions. The National Institute for Health and Care Excellence (NICE) did not find evidence that administering NSAIDs could increase the risk of developing COVID-19 or worsened the condition of COVID-19 patients. However, unwanted effects of specific drugs differ substantially in their occurrence and seriousness as well. It seemed to be for a long time that the NSAIDs provoked higher GI-risk was closely related to the COX1/COX2 selectivity, like the cardiovascular (CV) risk to the COX2/COX1 selectivity, however, the recent data did not prove it clearly. Based on the available literature while pondering the gastrointestinal and cardiovascular adverse events, among all NSAIDs the aceclofenac profile seemed to be the most favourable.]

Lege Artis Medicinae

[LAM 30: 1990–2020. Facing the mirror: Three decades of LAM, the Hungarian medicine and health care system]


Clinical Neuroscience

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.