Lege Artis Medicinae

[A part and the whole]

KAPÓCS Gábor

APRIL 20, 2003

Lege Artis Medicinae - 2003;13(03)

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Lege Artis Medicinae

[Severe acute respiratory syndrome]

BÁNHEGYI Dénes

Lege Artis Medicinae

[VIII. National Congress on Antibiotics]

SZÉKELY Éva

Lege Artis Medicinae

[Proteomics - the new challenge]

HUDECZ Ferenc

[The term ”proteome” (proteome, PROTEin complement to a genOME) by now a generally accepted expression in biomedical science meaning a complete complements of proteins. The discipline ”proteomics”, coined after proteome, deals with the analysis of the complete set of proteins occurring in the living organism. This includes the identification and quantification of proteins, the determination of protein localisation, modifications, interactions, activities and function. Performing comparative studies is an important part of proteomics for the analysis of proteins in health and disease. The knowledge generated is already used for improved diagnostic procedures and development of new drugs and therapies. During the proteome analysis, as outlined in this paper, even very small quantities (concentrations) of proteins are measured, then the protein is identified and its structure is elucidated. This procedure is followed by functional studies. An important part of proteomics is the collection and validation of numerical databases suitable for data mining. There is a general understanding that methodology driven research (e.g. NMR, mass spectrometry, DNA chips) is also an integrated part of this discipline. It is already sensed that the analysis of proteome can lead to the discovery of new proteins proving targets for drug research and to the establishment of new procedures with a perspective of improved diagnosis and therapy.]

Lege Artis Medicinae

[Benefit of combined clopidogrel-aspirin platelet aggregation inhibition in acute coronary syndrome and after percutaneous coronary angioplasty]

KELTAI Mátyás

[Platelet aggregation inhibition is equally important both in conservative and interventional cardiological treatment of acute coronary syndrome. Recently, results from three important trial were published. All three proved the efficacy of the combined aspirin + clopidogrel treatment. The basic results of the three clinical trials (CURE, PCI-CURE, CREDO) are summarized in the article. In the CURE trial the combined primary endpoint was reached in 11.4% of the patients in the control group and in 9.3% in the clopidogrel group. The relative risk reduction was 20%. The combined primary endpoint included CV mortality, MI and stroke. The treatment effect was mostly detectable in the prevention of MI and stroke. In the PCI-CURE trial 2658 patients of the CURE trial were analysed. All of them were treated by coronary angioplasty. In this group the primary endpoint (CV death, nonfatal MI, urgent revascularisation) was reached in 6.4% of the aspirin treated and in 4.5% of the aspirin + clopidogrel treated patients. The relative risk reduction was 30%. The CREDO trial investigated patients after coronary angioplasty. The indication of angioplasty was either acute or chronic. All patients received combined aspirin + clopidogrel but only for four weeks in the control group or for one year in the treatment group. The combined primary endpoint was decreased by 26.9%. In all the 3 trials the risk of bleeding was slightly but significantly increased by the combined aspirin + clopidogrel treatment. Clinical application: based on the results of the 3 trials it is concluded that combined aspirin + clopidogrel treatment is indicated in all patients with acute coronary syndrome, independently from the treatment strategy. The treatment should be continued for one year. This is also applicable for all patients treated with coronary angioplasty.]

Lege Artis Medicinae

[Extraintestinal manifestations in inflammatory bowel diseases]

LAKATOS László

[Inflammatory bowel diseases (IBD) are systemic disorders. Bowel symptoms are the predominant manifestations, however during the course of the disease a lot of intestinal and extraintestinal complications may occur. Systemic complications are responsible for substantial co-morbidity and they have negative influence on the quality of life. A part of the extraintestinal symptoms seem to have common pathogenetic background with IBD, while others are the consequences of subsequent metabolic and endocrine abnormalities or may relate to local complications and adverse effects of treatment. Growing evidence is available on the role of genetic and immunologic factors in the pathogenesis of extraintestinal manifestations. Most important systemic complications are: peripheral and axial arthritides, osteoporosis, uveitis, erythema nodosum, pyoderma gangraenosum, primary sclerosing cholangitis, nonalcoholic steatohepatitis, different types of anaemia, thromboembolism, kidney stones and urinary complications. Cooperation with the specialists is very important in the diagnosis and treatment of these comlications. During followup of IBD patients special attention is needed to monitor possible extraintestinal manifestations.]

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Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: A retrospective case-control study

NÉMETH Klára Zsófia, SZÛCS Anna , VITRAI József , JUHÁSZ Dóra , NÉMETH Pál János , HOLLÓ András

We aimed to investigate the association between fluoxetine use and the survival of hospitalised coronavirus disease (COVID-19) pneumonia patients. This retrospective case-control study used data extracted from the medical records of adult patients hospitalised with moderate or severe COVID-19 pneumonia at the Uzsoki Teaching Hospital of the Semmelweis University in Budapest, Hungary between 17 March and 22 April 2021. As a part of standard medical treatment, patients received anti-COVID-19 therapies as favipiravir, remdesivir, baricitinib or a combination of these drugs; and 110 of them received 20 mg fluoxetine capsules once daily as an adjuvant medication. Multivariable logistic regression was used to evaluate the association between fluoxetine use and mortality. For excluding a fluoxetine-selection bias potentially influencing our results, we compared baseline prognostic markers in the two groups treated versus not treated with fluoxetine. Out of the 269 participants, 205 (76.2%) survived and 64 (23.8%) died between days 2 and 28 after hospitalisation. Greater age (OR [95% CI] 1.08 [1.05–1.11], p<0.001), radiographic severity based on chest X-ray (OR [95% CI] 2.03 [1.27–3.25], p=0.003) and higher score of shortened National Early Warning Score (sNEWS) (OR [95% CI] 1.20 [1.01-1.43], p=0.04) were associated with higher mortality. Fluoxetine use was associated with an important (70%) decrease of mortality (OR [95% CI] 0.33 [0.16–0.68], p=0.002) compared to the non-fluoxetine group. Age, gender, LDH, CRP, and D-dimer levels, sNEWS, Chest X-ray score did not show statistical difference between the fluoxetine and non-fluoxetine groups supporting the reliability of our finding. Provisional to confirmation in randomised controlled studies, fluoxetine may be a potent treatment increasing the survival for COVID-19 pneumonia.

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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.

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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

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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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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.

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[The role of sleep in the relational memory processes ]

CSÁBI Eszter, ZÁMBÓ Ágnes, PROKECZ Lídia

[A growing body of evidence suggests that sleep plays an essential role in the consolidation of different memory systems, but less is known about the beneficial effect of sleep on relational memory processes and the recognition of emotional facial expressions, however, it is a fundamental cognitive skill in human everyday life. Thus, the study aims to investigate the effect of timing of learning and the role of sleep in relational memory processes. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. Our results suggest that the timing of learning and sleep plays an important role in the stabilizing process of memory representation to resist against forgetting.]