Lege Artis Medicinae

[Medical treatment of Alzheimer-disease]

TARISKA Péter

FEBRUARY 20, 2003

Lege Artis Medicinae - 2003;13(02)

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Lege Artis Medicinae

[Human genome project]

SASVÁRI-SZÉKELY Mária

[The main goal of the Human Genom Project is to reveal the complete structure of the human DNA, involving the sequence determination of the three billion basepairs. The program was launched in 1990, executed in laboratories of the public sector in several countries. Results of this project are made public on the Internet. In 1998 a private sector company, Celera, was founded with the same goal. In 2001 both projects announced the accomplishment of the first draft of the Human Genome. A whole issue of Nature and Science magazine was devoted to present the first results of their findings. According to the results less than one percent of the genetic information is transcribed to proteins. The estimated number of genes was also lower than expected (30-40 thousand, which number recently increased to 40-60 thousand). Based on these findings, human complexity should be ascribed to the variability of the information units (domains) rather than to the number of genes. Once the complete sequence of the humane genome is accomplished, the ’pre-genomic era’ will be over and the ’post-genomic era’ will begin, dealing with understanding the genetic information, annotating the genes and mapping the genetic variability of people.]

Lege Artis Medicinae

[Will the reform in the Hungarian health care be realized?]

FRENKL Róbert

Lege Artis Medicinae

[A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol]

SZILASI Mária

Lege Artis Medicinae

[New molecular based methods for diagnosis, classification and prognosis of leukemias]

ZVARA Ágnes, HACKLER László ifj., PUSKÁS László G.

[Normal functions of the cell are based on the precise regulation of various genes. If this strict regulation and the hierarchy of genes becomes upset due to some flaws of the system, the result will be cellular dysfunction which may eventually lead to carcinogenic transformation. The two main challenges in the classification of cancers are the discovery of new molecular markers characteristic to defined disease groups and the classification of already diagnosed or new cases into existing groups. This precise classification may open the door to tailored treatment or project the expected outcome of the disease. Today, there is unlimited access available to the databases containing sequences and localisation of the genes within the confines of Human Genome project. It provides significant help for the discovery of chromosome abnormalities and systematic analysis of gene expression patterns. This is important not only to understand normal functions of the cells, but it also contributes to the identification of new genes that are characteristic to given disease groups as markers and that are potential drug targets. Until the second half of the twentieth century the study of the function and regulation of genes was based on step by step investigation of individual genes. The fact that the genomes of an increasing number of organisms have become identified in whole or in part, numerous new techniques have been developed facilitating the systematic analysis of gene functions. The aim of this study is to summarise the new, molecular based possibilities for classification, diagnosis and prognosis of cancers, as well as to summarise the results of these areas, primarily from the point of view of leukemias.]

Lege Artis Medicinae

[Diuretic treatment]

RADÓ János

[Diuretics are used almost in all fields of medical practice for treating patients in various conditions associated with or without oedema. They exert their effects through profound alterations in the fluid volumes, ion content of the body and in the osmoregulation. They act mainly on the kidneys but the functions of several other organs are also influenced including the heart and vessels, the lungs, liver and the brain. Summarising our knowledge on the diuretics is justified by the broadened use of these drugs and the differences regarding their site of action, potency, way of administration, dosing and side effects. The special indications for diuretic therapy and combined usage of different diuretics are also reviewed.]

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Clinical Neuroscience

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

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.

Hypertension and nephrology

[About the care of patients with hyperuricaemia and gout]

[This consensus document is intended to provide guidance for the effective and efficient treatment of asymptomatic individuals with high uric acid levels and gout patients.]

Clinical Neuroscience

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]

Clinical Neuroscience

Creutzfeldt-Jakob Disease: A single center experience and systemic analysis of cases in Turkey

USLU Ilgen Ferda, ELIF Gökçal, GÜRSOY Esra Azize, KOLUKISA Mehmet, YILDIZ Babacan Gulsen

We aimed to analyze the clinical, laboratory and neuroimaging findings in patients with sporadic Creutzfeldt-Jakob disease (CJD) in a single center as well as to review other published cases in Turkey. Between January 1st, 2014 and June 31st, 2017, all CJD cases were evaluated based on clinical findings, differential diagnosis, the previous misdiagnosis, electroencephalography (EEG), cerebrospinal fluid and cranial magnetic resonance imaging (MRI) findings in our center. All published cases in Turkey between 2005-2018 were also reviewed. In a total of 13 patients, progressive cognitive decline was the most common presenting symptom. Two patients had a diagnosis of Heidenhain variant, 1 patient had a diagnosis of Oppenheimer-Brownell variant. Seven patients (53.3%) had been misdiagnosed with depression, vascular dementia, normal pressure hydrocephalus or encephalitis. Eleven patients (87%) had typical MRI findings but only 5 of these were present at baseline. Asymmetrical high signal abnormalities on MRI were observed in 4 patients. Five patients (45.4%) had periodic spike wave complexes on EEG, all appeared during the follow-up. There were 74 published cases in Turkey bet­ween 2005 and 2018, with various clinical presentations. CJD has a variety of clinical features in our patient series as well as in cases reported in Turkey. Although progressive cognitive decline is the most common presenting symptom, unusual manifestations in early stages of the disease might cause misdiagnosis. Variant forms should be kept in mind in patients with isolated visual or cerebellar symptoms. MRI and EEG should be repeated during follow-up period if the clinical suspicion still exists.