Lege Artis Medicinae

[Disease in times of crisis]

BÁNFALVI Attila, CSÖRSZ Ilona

JANUARY 20, 2012

Lege Artis Medicinae - 2012;22(01)

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[Genetic background of thyroid cancers]

HALÁSZLAKI Csaba, LAKATOS Péter, KÓSA P. János, BALLA Bernadett, JÁRAY Balázs, TAKÁCS István

[Molecular genetics has become an indispensable diagnostic tool in a number of diseases. The most frequent thyroid tumours are associated with genetic alterations that might be used for diagnostic purpose in the future. Somatic mutations and rearrangements in BRAF, RAS family RET/PTC and PAX8/PPAR-gamma genes may occur in papillary and follicular thyroid carcinomas. Other mutations of the RET gene can be found in medullary carcinomas (in sporadic as well as hereditary types), whereas mutations of the genes TP53, RAS, and BRAF are associated with poorly differentiated and anaplastic carcinomas. At present, the most reliable diagnostic tool for the differential diagnosis of thyroid nodules is fine-needle aspiration cytology. However, the existing malignancy cannot be unequivocally proven in up to 10-40% of all samples. On the basis of previous results, genetic examination of fine needle aspiration samples from thyroid nodules can contribute to a more precise diagnosis and the timely removal of potentially malignant nodules.]

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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

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.

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Electrophysiological investigation for autonomic dysfunction in patients with myasthenia gravis: A prospective study

NALBANTOGLU Mecbure, AKALIN Ali Mehmet, GUNDUZ Aysegul, KIZILTAN Meral

Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Autonomic dysfunction is not a commonly known association with MG. We conducted this study to evaluate autonomic functions in MG & subgroups and to investigate the effects of acetylcholinesterase inhibitors. This study comprised 30 autoimmune MG patients and 30 healthy volunteers. Autonomic tests including sympathetic skin response (SSR) and R-R interval variation analysis (RRIV) was carried out. The tests were performed two times for patients who were under acetylcholinesterase inhibitors during the current assessment. The RRIV rise during hyperventilation was better (p=0.006) and Valsalva ratio (p=0.039) was lower in control group. The SSR amplitudes were lower thereafter drug intake (p=0.030). As much as time went by after drug administration prolonged SSR latencies were obtained (p=0.043).Valsalva ratio was lower in the AchR antibody negative group (p=0.033). The findings showed that both ocular/generalized MG patients have a subclinical parasympathetic abnormality prominent in the AchR antibody negative group and pyridostigmine has a peripheral sympathetic cholinergic noncumulative effect.

Lege Artis Medicinae

[Diagnosis and treatment of microvascular coronary heart disease. Specialities of conditions in Hungary]

SZAUDER Ipoly

[Invasive investigations show that in two-thirds of patients the myocardial ischaemia persists without obstructive coronary disease and any other heart conditions (INOCA). The underlying cause may be microvascular dysfunction (CMD) with consecutive microvascular coronary disease (MVD) and microvascular or epicardial vasospastic angina (MVA). The modern practice of clinical cardiology while using the developed non-invasive cardiac imaging permits exact measuring of the coronary flow with its characteristic indices. All of these improve the diagnosing of CMD-induced myocardial ischemia and provide opportunity to determine primary MVD cases. Since the recognition and treatment of MVD is significantly underrep­resented in the Hungarian medical care, the primary stable microvascular angina (MVA) is described in detail below with its modern invasive and non-invasive differential diagnosis and treatment, concerning especially its frequency provoked by high blood pressure and female coronary heart diseases. There are highlighted all recommended diagnostic procedures available under domestic conditions.]

Lege Artis Medicinae

[Second game, 37th move and Fourth game 78th move]

VOKÓ Zoltán

[What has Go to do with making clinical decisions? One of the greatest intellectual challenges of bedside medicine is making decisions under uncertainty. Besides the psychological traps of traditionally intuitive and heuristic medical decision making, lack of information, scarce resources and characteristics of doctor-patient relationship contribute equally to this uncertainty. Formal, mathematical model based analysis of decisions used widely in developing clinical guidelines and in health technology assessment provides a good tool in theoretical terms to avoid pitfalls of intuitive decision making. Nevertheless it can be hardly used in individual situations and most physicians dislike it as well. This method, however, has its own limitations, especially while tailoring individual decisions, under inclusion of potential lack of input data used for calculations, or its large imprecision, and the low capability of the current mathematical models to represent the full complexity and variability of processes in complex systems. Nevertheless, clinical decision support systems can be helpful in the individual decision making of physicians if they are well integrated in the health information systems, and do not break down the physicians’ autonomy of making decisions. Classical decision support systems are knowledge based and rely on system of rules and problem specific algorithms. They are utilized widely from health administration to image processing. The current information revolution created the so-called artificial intelligence by machine learning methods, i.e. machines can learn indeed. This new generation of artificial intelligence is not based on particular system of rules but on neuronal networks teaching themselves by huge databases and general learning algorithms. This type of artificial intelligence outperforms humans already in certain fields like chess, Go, or aerial combat. Its development is full of challenges and threats, while it presents a technological breakthrough, which cannot be stopped and will transform our world. Its development and application has already started also in the healthcare. Health professionals must participate in this development to steer it into the right direction. Lee Sedol, 18-times Go world champion retired three years after his historical defeat from AlphaGo artificial intelligence, be­cause “Even if I become the No. 1, there is an entity that cannot be defeated”. It is our great luck that we do not need to compete or defeat it, we must ensure instead that it would be safe and trustworthy, and in collaboration with humans this entity would make healthcare more effective and efficient. ]