Lege Artis Medicinae

[ANTICOAGULATION AND THROMBOEMBOLIC DISEASES - INDICATIONS, PROBLEMS AND PRACTICAL ASPECTS]

SAS Géza

APRIL 21, 2004

Lege Artis Medicinae - 2004;14(04)

[The widespread application of the LMW heparins promoted the prevention and therapy of the thromboembolic diseases in Hungary. Their propagation is mainly due to their simple clinical application and the active promotion of the producing pharmaceutical companies. However, the recommended “unnecessary” (in the reality the lack of) laboratory control may cause severe complications (bleeding, thromboembolism etc.) sometimes especially at the therapeutic application. For this reason, unfractionated (UF) heparin is advised in case of acute deep vein thrombosis when a patient is in the particular danger of bleeding because of its better controllability and the opportunity to stop anticoagulation immediately. In recent years, the indication of the long-term anticoagulation therapy expanded significantly. The number of patients is ever growing who need continuous anticoagulation because of atrial fibrillation or venous thromboembolic episode taken place earlier. Large randomised multicenter trials proved the efficacy of prolonged coumarin therapy in the prevention of recurrence of thromboembolic episodes in these diseases. Due to its advantageous pharmacological characteristics warfarin is especially suitable for the attainment of continuous anticoagulation. The direct thrombin inhibitor melagatran (and its orally applicable form, ximelagatran) may open a new era in the prophylaxis and therapy of the thromboembolic diseases. Its advantageous pharmacological characteristics and its simple application may make them to the antithrombotics of the future in case of a reasonable price and/or subsidisation.]

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Lege Artis Medicinae

[THE PROSPECTS OF SURGICAL TREATMENT OF END-STAGE EMPHYSEMA (COPD): THE LUNG VOLUME REDUCTION SURGERY]

KECSKÉS László

[On the basis of relevant international literature the author presents the indications, contraindications, risks and results of the lung volume reduction surgery applicable in cases of therapyresistant end-stage COPD. These interventions, which require strong interdisciplinary cooperation of a pneumonologist, a thoracic surgeon, an anaesthesiologist and a physiotherapeutist were introduced in 1995 as a result of Cooper's study. A multicentric prospective study analysed the efficiency of this new surgical procedure. The results were evaluated in 2003 and it is important to be emphasised that in short term (3-6 months) and medium term (2-4 years) an improvement of lung function and of the quality of life can be observed in those patients who have heterogeneous emphysema, mainly in the upper lobe. Also, in case of homogenous emphysema this surgical procedure can be effective but perioperative mortality is higher and a deterioration in the health-state can occur as soon as six month after the intervention. The follow-up analyses of COPD patients with alpha- 1 antitrypsin deficiency show similarly moderate results. In Szombathely, Hungary 67 such interventions were carried out on 55 patients between 1997 and 2002, with a 4.4 % mortality rate which corresponds the international standard. Our own experience also supports the fact that in short and medium term the FEV1, RV, paO2, paCO2 and the quality of life take a positive change, the continuous O2-demand of patients will cease to exist and they regain parts of the former activity. The LVRS bears remarkable cost due to the use of staplers and surgical materials as well as longer hospital stay with the need of intensive care unit. Today in Hungary the LVRS is a realistic alternative in case of severe COPD to lung transplantation. The cost of an LVRS is maximum 10% of a lung transplantation. Patients having undergone an LVRS as well as patients unacceptable for LVRS may be suitable for lung transplantation.]

Lege Artis Medicinae

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Lege Artis Medicinae

[HUMAN DENDRITIC CELLS AND INFECTIVE AGENTS]

KIS Zoltán

[Dendritic cells represent important components of the innate and adaptive immune responses. Human dendritic cells can be divided into two major subsets: myeloid and plasmacytoid (lymphoid) dendritic cells. The unique function of the dendritic cells is to capture antigens, present and to activate the antigenic peptides to the T lymphocytes. Dendritic cells go through a maturation process both in vitro and in vivo. By the use of pathogenrecognition- receptors the immature dendritic cells sense diverse pathogens or their various components, or cellular factors produced by the infected neighboring non-dendritic cells, and maturation signals are transduced for the dendritic cells. The heterogeneity of the pathogen-recognition-receptors and the microbial stimuli initiate a broad range of interactions between dendritic cells and infectious agents. Dendritic cells infected with certain viruses produce only a few infectious particles, but express and present viral antigens to T lymphocytes and immune response is initiated (influenza virus). Dendritic cells infected with certain pathogens not only initiate immune response but also disseminate the pathogen (human immunodeficiency virus, Mycobacterium tuberculosis). Some pathogens are killed in the dendritic cells, but the antigens are presented to the T cells, and immune responses are induced (Chlamydia trachomatis and Chlamydia psittaci). Dendritic cells capture antigens produced by infected neighbouring cells and present them to T lymphocytes, thus immune response is initiated (human cyto-megalovirus, herpes simplex virus). Dendritic cells are responsible for virus-induced immunosupp-ression; dendritic cells infected with certain pathogens form syncytia with T cells, thereby contribute to the suppression of T cell functions directed against opportunistic infections (measles virus). Dendritic cells can present not only foreign antigens but also self-antigens and when immature dendritic cells become mature upon exposure to inflammatory processes or to pathogens capable of activating them they can induce autoimmunity.]

Lege Artis Medicinae

[Preliminary concept of the bill on protecting personal genetic data, on genetic research, on genetic test, screening, and on the biobanks]

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Lege Artis Medicinae

[THE IMPORTANCE OF HYPERTENSION IN CEREBROVASCULAR DISEASES]

SZAPÁRY László

[Stroke is a highly prevalent disorder worldwide; it is the third main cause of death and the leading cause of severe disability. Recent data showed that 72-86% of cerebrovascular disorders are of ischaemic type. Arterial hypertension is the most prevalent risk factor for both haemorrhagic and ischaemic stroke, it is present in approximately 70% of cases. All forms of hypertension, isolated systolic or diastolic and combined hypertension increase stroke risk about 3-4 times and the relationship with systolic blood pressure may even be stronger than with diastolic blood pressure. Hypertension is very common after acute stroke. In this phase the cerebral autoregulation is disturbed in the region of focal brain ischaemia or haemorrhage such that cerebral blood flow is directly dependent on systemic blood pressure. It is therefore essential to avoid systemic hypotension in acute stroke patients and the reduction of high blood pressure may lower cerebral blood flow in the ischemic penumbra. Evidence from clinical data shows that control of blood pressure leads to lower risk of first or reccurent stroke and patients have shown beneficial effects especially of ACE inhibitors and diuretics. In the PROGRESS study both hypertensive and non-hypertensive cerebrovascular patients benefited from antihypertensive therapy. Previous results suggests that there may be additional beneficial effects of the ACEinhibitor therapy not related to blood pressure lowering in the prevention of stroke.]

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[Actual questions of the longterm anticoagulant therapy]

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[In the last few years we have witnessed some changes in the area of the chronic oral anticoagulant therapy. The nomenclature of the anticoagulant drugs has been modified and concern has arisen about the possible vascular calcification in patients on long-term warfarin therapy. Because of the novelty of the “new” anticoagulants (dabigatran etc.) has been lost, instead of their previous acronym (NOAC) the DOAC (direct oral anticoagulants) term has been accepted for their marking. Experimental and clinical data suggested that vitamin K-antagonists (VKA) in addition to the coagulation factors disturb the production of other proteins, too. By inhibiting the matrix Gla protein (MGP), the chronic warfarin therapy promotes the calcification in media of the arteries as it was shown in women participating in routine mammography. However, the clinical importance of this observation is dubious, because the incidence of acute coronary events is not increased in cases of warfarin therapy in patients with atrial fibrillation. Notwith­standing, in addition to the bleeding complications we have to take into account of the possible harmful vascular calcification, too, at the indication of chronic coumarin therapy. Therefore, this therapy should be applied only in proper cases, such as non-valvular atrial fibrillation with a high risk of ischaemic stroke or unprovoked venous thromboembolic disease with a high risk of recurrence. The results of the Swedish anticoagulant register show that the efficacy and safety of the well-managed coumarin therapy may be superior to the treatments with DOACs. However, DOACs are indispensable in certain cases in which a previous “probe” coumarin treatment is unfounded.]

Clinical Neuroscience

Cases of inborn errors of metabolism diagnosed in children with autism

CAKAR Emel Nafiye, YILMAZBAS Pınar

Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism. One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. The personal information, routine and specific metabolic tests of the patients were analyzed retrospectively. Out of the 3261 patients who presented to our outpatient clinic, 179 (5.48%) were diagnosed with autism spectrum disorder and were included in the study. As a result of specific metabolic examinations performed, 6 (3.3%) patients were diagnosed with inborn errors of metabolism. Two of our patients were diagnosed with classical phenylketonuria, two with classical homocystinuria, one with mucopolysaccharidosis type 3D (Sanfilippo syndrome) and one with 3-methylchrotonyl Co-A carboxylase deficiency. Inborn errors of metabolism may rarely present with autism spectrum disorder symptoms. Careful evaluation of the history, physical examination and additional findings in patients diagnosed with autism spectrum disorder will guide the clinician in the decision-making process and chose the appropriate specific metabolic investigation. An underlying inborn errors of metabolism may be a treatable cause of autism.

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

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.