Lege Artis Medicinae

[Gastrointestinal Protective Efficacy of Esomeprazole Comparative Studies in the International Literature]

NOVEMBER 30, 2004

Lege Artis Medicinae - 2005;15(01 klsz)

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Lege Artis Medicinae

[NOVEL ASPECTS OF COX-2 SELECTIVE NON-STEROIDAL ANTI-INFLAMMATORY DRUG THERAPY]

MŰZES Györgyi

[The cyclooxygenase (COX) metabolic pathway and prostaglandin production appear to play a causal role in the promotion and progression of human cancers. Recently COX-2 has received a great deal of interest since it is frequently overexpressed in a wide spectrum of cancers and precancerous lesions. Furthermore, elevated production of prostanoids (particularly PGE2) via COX-2 is associated with several pro-carcinogenic effects including increased proliferation, apoptosis resistance, tumor neoangiogenesis and invasiveness, host immunosuppression, and altered xenobiotic metabolism. Inhibitors of COX-1 and COX-2 (aspirin and most other nonsteroidal anti-inflammatory drugs) and of COX-2 alone (e.g. coxibs) have shown cancer preventive efficacy in epidemiological studies, experimental studies and in human clinical trials. Due to their improved side effect profile, COX-2 selective inhibitors appear to hold substantial promise for long-term administration in the setting of cancer prevention. Emerging data suggest that these agents may have potential in cancer treatment as well. In addition recent results indicate that COX-2 enzyme is also overexpressed in inflammatory processes of the central nervous system, e.g. in Alzheimer’s disease, so its suppression could offer a possible new therapeutic strategy even in the prevention and treatment of Alzheimer’s disease.]

Lege Artis Medicinae

[GASTROINTESTINAL COMPLICATIONS OF LOW-DOSE ASPIRIN TREATMENT]

RÁCZ István

[Since its synthesis more than 100 years ago aspirin has become one of the most successful drug. Low-dose, long-term aspirin therapy reduces the risk of myocardial infarction, the frequency of cerebral stroke and also reduces the mortality of peripheral arterial diseases and systemic embolisms. With aspirin therapy becoming more and more widespread current knowledge is also getting more concerned about the gastrointestinal risks and beneficial effects. Aspirin therapy causes gastrointestinal damages by the inhibition of endogenous prostaglandin synthesis. The ion trapping effect and the injury of mucosal barrier as well as the inhibition of platelet aggregation are also responsible for gastrointestinal damages. According to epidemiological studies lowdose aspirin treatment increases the risk of acute upper gastrointestinal bleeding by 1.5-2.0 fold. However, endoscopic studies indicate that gastroduodenal ulcers may develop even in 10 percent of cases on long term aspirin treatment, most frequently in a symptom-free form. Older age as well as Helicobacter pylori infection increase the risk of aspirin induced ulcers. Beside Helicobacter pylori eradication therapy, preventive proton-pump-inhibitor treatment and the widespread of new non-toxic aspirin derivates may decrease the risk of gastrointestinal complications. Capsule endoscopy also seems to be a promising diagnostic tool for detecting aspirin induced small bowel erosions and ulcers. Long-term aspirin treatment increases the risk of acute bleeding from large bowel diverticulas especially with non-steroidal anti-inflammatory drug co-therapy present. Long-term, low-dose aspirin treatment is a promising method for the chemoprevention of colorectal cancers.]

Lege Artis Medicinae

[Changes to Gastroenterology Specialist Training Following Hungary’s Accession to the European Union]

LONOVICS János

Lege Artis Medicinae

[FROM ASPIRIN TO COXIBS - JANUS-FACE OF THE NONSTEROIDAL ANTI-INFLAMMATORY THERAPY]

NEMESÁNSZKY Elemér

[Since the introduction of aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) proved to be the most commonly used drugs in the world. One of the major factors limiting their use is gastrointestinal toxicity. It has long been recognised that NSAID use is associated with serious, sometimes life-threatening adverse effects, like gastrointestinal ulcers, bleeding and perforation. Recent studies have indicated that the combination of NSAID and aspirin significantly increases the risk of complications. Aspirin is like a two-edged sword, balancing cardiovascular prevention with the risk of gastrointestinal side effects. Past history of ulcer carries the highest individual risk and other contributing factors include age, concurrent anticoagulation, cortocisteroid therapy, as well as high-dose or multipleforms of NSAID use. The mechanism of action of NSAID is to inhibit prostaglandin production through cyclooxygenase (COX). The inhibition of COX-2 isoenzyme reduces inflammatory-mediated prostaglandins, while the inhibition of COX-1 reduces the level of prostaglandins needed for normal protecting mechanism of the gastric mucosa. Non-selective NSAID has impact on both COX-enzymes, while selective COX-2-inhibitors (such as coxibs) exert their effects without affecting mucosal defence significantly. It is important to note that the risk of complications can not be reduced to zero by any therapeutic approach. The most appropriate treatment modality is to administer PPI co-therapy for the sake of gastro-protection, especially in high-risk cases. Histamine-2-receptor antagonists are not effective in reducing ulcer and complication in that particular group of patients. It has turned out that the inhibition of the synthesis of COX-2 by rofecoxib increases the risk of developing thromboembolic events and myocardial infaction. This has led to the withdrawal of Vioxx from the market on 30. 09. 2004. Studies conducted in recents years shed new light on numerous beneficial effects of NSAID other than alleviate pain, cure inflammatory processes and diminish higher temperature. The incidence of colon polyps and adenomas as well as cancers is reduced among people who are on maintanance NSAID therapy. The process of stone formation in the biliary tract is also reduced in patients who are on NSAID treatment. Development of Alzheimer's disease seems to be hindered, however, this finding can not yet be considered as evidence based.]

Lege Artis Medicinae

[PHARMACEUTICAL PREVENTION OF THE UPPER GASTROINTESTINAL SIDE-EFFECTS OF NSAID THERAPY]

HERSZÉNYI László, TULASSAY Zsolt

[Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain and inflammation in patients with rheumatoid arthritis and osteoarthritis. However, they are also associated with a significant risk of gastrointestinal events with clinical and economic consequences. It is mandatory to rationalise the use of different NSAID treatment strategies in patients with varying degrees of gastrointestinal and cardiovascular risk. In patients for those aged <65 years with no previous gastrointestinal event and not concurrently on aspirin (low risk patients), the use of an NSAID should be considered as appropriate. For patients with a previous gastrointestinal event (high risk patients) or who concurrently received aspirin, an NSAID alone should be rated as inappropriate and either a coxib or selective cyclooxygenase-2 inhibitor, or an NSAID + proton pump inhibitor combination is considered as appropriate. Finally, for patients aged >65 years with a previous gastrointestinal event and on aspirin (patients with very high risk) a coxib in conjunction with a proton pump inhibitor is considered to be the best therapeutic strategy.]

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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.

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Neuroscience highlights: Main cell types underlying memory and spatial navigation

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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.

Clinical Neuroscience

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Delirium is a syndrome frequently encountered in intensive care and associated with a poor prognosis. Intensive care delirium is mostly based on general and palliative intensive care data in the literature. In this study, we aimed to investigate the incidence of delirium in coronary intensive care unit (CICU), related factors, its relationship with inhospital and follow up prognosis, incidence of age-related delirium and its effect on outcomes. This study was conducted with patients hospitalized in CICU of a tertiary university hospital between 01 August 2017 and 01 August 2018. Files of all patients were examined in details, and demographic, clinic and laboratory parameters were recorded. Patients confirmed with psychiatry consultation were included in the groups of patients who developed delirium. Patients were divided into groups with and without delirium developed, and baseline features, inhospital and follow up prognoses were investigated. In addition, patients were divided into four groups as <65 years old, 65-75 yo, 75-84 yo and> 85 yo, and the incidence of delirium, related factors and prognoses were compared among these groups. A total of 1108 patients (mean age: 64.4 ± 13.9 years; 66% men) who were followed in the intensive care unit with variable indications were included in the study. Of all patients 11.1% developed delirium in the CICU. Patients who developed delirium were older, comorbidities were more frequent, and these patients showed increased inflammation findings, and significant increase in inhospital mortality compared to those who did not develop delirium (p<0.05). At median 9-month follow up period, rehospitalization, reinfarction, cognitive dysfunction, initiation of psychiatric therapy and mortality were significantly higher in the delirium group (p<0.05). When patients who developed delirium were divided into four groups by age and analyzed, incidence of delirium and mortality rate in delirium group were significantly increased by age (p<0.05). Development of delirium in coronary intensive care unit is associated with increased inhospital and follow up morbidity and mortality. Delirium is more commonly seen in geriatric patients and those with comorbidity, and is associated with a poorer prognosis. High-risk patients should be more carefully monitored for the risk of delirium.

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