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Clinical Oncology

APRIL 30, 2020

[Coronavirus pandemic – new challenges in oncotherapy]

MINÁROVITS János

[This review outlines some of the basic observations related to coronaviruses infecting animals and describes – in a nutshell – the characteristics of human coronaviruses causing mild or severe respiratory diseases in infected individuals. A special attention is given to SARS-CoV-2, the causative agent of the current coronavirus disease (Covid-19) pandemic, and to the pathomechanism of severe acute respiratory syndrome (SARS) which is also accompanied with multiorgan failure in a subset of infected patients. Recently discovered unique molecular features of SARS-CoV-2 are described as well. These molecular cues may affect human to human virus transmission whereas they are absent, remarkably, from the other lung-targeting highly pathogenic human coronaviruses (SARS-CoV-1 and MERS-CoV) which did not spread all over the world. The possibilities of active immunization to prevent SARS-CoV-2 infection and the development of selective small molecule inhibitors curbing the replication of the virus are also touched upon. The review closes with a few remarks regarding the Hungarian and international recommendations concerning the treatment of SARSCoV- 2 infected cancer patients.]

Clinical Oncology

DECEMBER 30, 2019

[Systemic anticancer therapy in patients undergoing hemodialysis]

VÉGH Éva, LAKATOS Gábor, TOKODI Zsófia

[The number of cancer patients receiving regular dialysis treatment is increasing. These patients could benefi t similarly from the regular anticancer therapies. Data of the use of antineoplastic therapies in this vulnerable patient population mainly come from case reports and small case series. The lack of knowledge and lack of practical experiences in this patient group may lead to suboptimal cancer treatment. Defi ning the indication for antineoplastic treatment and choosing the appropriate drug is a challenging task and the patients’ prognosis and quality of life aspects should be evaluated carefully. The timing of anticancer treatment and the dialysis is also an important issue in this decision-making process. Close cooperation between the oncologists and nephrologists is essential in the proper antineoplastic treatment of the dialysed patients.]

Lege Artis Medicinae

SEPTEMBER 30, 2020

[The pain-trigger role of cytokines in the nervous system – the direct analgesic effect of anti-cytokine therapy ]

HODINKA László, VERECKEI Edit

[Nociceptive, neuropathic and central me­chanisms are involved in the perception, transmission and processing of chronic pain and shaping of cerebral pain image. Alar­mins – molecules alarming defence and signing the presence of pathogens and tissue damage - trigger a series of pathogenic events resulting in inflammatory pain stimuli. Proinflammatory cytokines play a determining role in the pain perception at the level of the nervous system. Continuous inflammatory stimuli while sensitizing the periferic and central neurons activate the pain-related cerebral areas and develop the complex pain image, the pain matrix. Ce­reb­ral functional connections are operating in networks and can be visualized by functional MRI. Cytokines activate the neurons directly or indirectly by other neuromediators. Cytokine receptors are expressed on no­ciceptors and even on higher-level neurons and on various non-neural cells, such as microglia and astrocytes. The most ubiquitous cytokines are the Tumour Necrosis Factor and Interleukin 6 in the nervous sys­tem. The signaling pathways are the Nuclear Factor κB and the Janus-kinase enzyme system. The proinflammatory cytokines and the Janus-kinase are therefore primary therapeutic targets. Anti-cytokine biologicals and small molecular kinase inhibitors decrease the pain and improve functional activity in rheumatoid arthritis. Decrease of pain was more pronounced than expected only from the decrease of the clinical biomarkers of inflammation. The early and ra­pid painkiller effect of targeted biological and chemical-biological response modifiers is attributed to their direct analgesic effect on the brain.]

Clinical Neuroscience

JULY 30, 2020

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

TOLVAJ Balázs, HAHN Katalin, NAGY Zsuzsanna, VADVÁRI Árpád, CSOMOR Judit, GELPI Ellen, ILLÉS Zsolt, GARZULY Ferenc

Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

Clinical Neuroscience

JULY 30, 2020

Extraskeletal, intradural, non-metastatic Ewing’s sarcoma. Case report

OTTÓFFY Gábor, KOMÁROMY Hedvig

Intracranial localization of Ewing’s sarcoma is considerably very rare. Herein, we present clinical and neuroimaging findings regarding a 4-year-old boy with intracranial Ewing’s sarcoma. He was born prematurely, suffered intraventricular haemorrhage, posthaemorrhagic hydrocephalus developed, and a ventriculoperitoneal shunt was inserted in the newborn period. The patient endured re­gular follow ups, no signs of shunt malfunction nor increased intracranial pressure were observed. The last neuroima­ging examination was performed at 8 months of age. Upon reaching the age of 4 years, repeated vomiting and focal seizures began, and symptoms of increased intracranial pressure were detected. A brain MRI depicted a left frontoparietal space-occupying lesion infiltrating the superior sagittal sinus. The patient underwent a craniotomy resulting in the total excision of the tumour. The histological examination of the tissue revealed a small round blue cell tumour. The diagnosis was confirmed by the detection of EWSR1 gene translocation with FISH (fluorescent in situ hybridization). No additional metastases were detected during the staging examinations. The patient was treated in accordance to the EuroEwing 99 protocol. Today, ten years onward, the patient is tumour and seizure free and has a reasonably high quality of life.

Clinical Neuroscience

JANUARY 30, 2020

[The quality of life of the cluster headache patients during the active phase of the headache]

DIÓSSY Mária, BALOGH Eszter, MAGYAR Máté, GYÜRE Tamás, CSÉPÁNY Éva, BOZSIK György, ERTSEY Csaba

[Introduction - Cluster headache (CH), which affects 0.1% of the population, is one of the most painful human conditions: despite adequate treatment, the frequent and severe headaches cause a significant burden to the patients. According to a small number of previous studies, CH has a serious negative effect on the sufferers’ quality of life (QOL). In the current study, we set out to examine the quality of life of the CH patients attending our outpatient service between 2013 and 2016, using generic and headache-specific QOL instruments. Methods - A total of 42 CH patients (16 females and 26 males; mean age: 39.1±13.5 years) completed the SF-36 generic QOL questionnaire and the headache- specific CHQQ questionnaire (Comprehensive Headache- related Quality of life Questionnaire), during the active phase of their headache. Their data were compared to those of patients suffering from chronic tension type headache (CTH) and to data obtained from controls not suffering from significant forms of headache, using Kruskal-Wallis tests. Results - During the active phase of the CH, the patients’ generic QOL was significantly worse than that of normal controls in four of the 8 domains of the SF-36 instrument. Apart from a significantly worse result in the ‘Bodily pain’ SF-36 domain, there were no significant differences between the CH patients’ and the CTH patients’ results. All the dimensions and the total score of the headache-specific CHQQ instrument showed significantly worse QOL in the CH group than in the CTH group or in the control group. Conclusion - Cluster headache has a significant negative effect on the quality of life. The decrease of QOL experienced by the patients was better reflected by the headache-specific CHQQ instrument than by the generic SF-36 instrument. ]

Lege Artis Medicinae

JANUARY 20, 2020

[History of Daytime Hospital of the Department of Psychiatry in the University of Debrecen ]

ÉGERHÁZI Anikó, CSERÉP Edina, MAGYAR Erzsébet

[In Hungary, there was a ward related psychotherapy already since the 1960s, yet without any national network to the 1980s. In Debrecen the spreading of the psychotherapeutic approach started in the psychiatric facilities since the 1990s. Daytime Hospital was founded first in the County Hospital and later on in the Department of Psychiatry of the University. The latter option was provided by separating the psychiatry from neurology. This study presents the development of the day care at the Psychiatric Department along the opportunities and shows the structure of the actually functioning system finally reports on our future plans respectively. Initially started the occupational therapy, gymnastics, community cooking and walking, which did not require any separate rooms. The 22-bed psychotherapeutic unit was established 2014 with its joined capacity for 11 persons in the Daytime Hospital. The County Hospital is engaged primarily in socio-therapy of psychotic psychiatry pa­tients, however the Psychiatric Department is rehabilitating mainly patients with affective spectrum disorders. Patients are treated in socio-therapy and psychotherapy small groups for a half or one year. Afterward they enter the outpatient program, may join the Patient Club or decide for therapeutic occupation aiming the best way of recovery. According to the feedback, there is a long-term change in the mental state of the patients leading to improvement in their quality of life, which we plan to prove by an efficacy research program. ]

Clinical Oncology

FEBRUARY 20, 2019

[Liquid biopsy in clinical oncology – fine-tuning precision medicine]

PRISKIN Katalin, PINTÉR Lajos, JAKSA Gábor, PÓLYA Sára, KAHÁN Zsuzsa, SÜKÖSD Farkas, HARACSKA Lajos

[The classical method of genetically characterising a tumour requires tissue biopsy with which a small sample is removed from the affected organ. This sample represents the tumour in the further analyses. However, the localised nature of sample collection limits representative characterisation. The so-called circulating tumour DNA, isolated from blood plasma after a simple sample collection, potentially enables the oncological analysis of all tumour tissues carrying genetic alterations that can be identifi ed as markers. In order to maximally exploit the potentials of circulating tumour DNA, we must adjust the analytical tools to its specifi c features. The preanalytical handling and storage of the sample signifi cantly infl uences its further usability. In order to be able to detect a potential mutation in a mostly wild-type background, the development of new, specifi c methods is needed, most of which are based on next-generation sequencing techniques. In the past decades, the pronounced decrease in the costs of such techniques led to an accumulation of an immense amount of genetic information on tumorigenesis. Due to the development of sequencing technologies, the turnaround times of tests also decreased enabling their employment in routine care besides research. Starting from our research, this can be realised via three approaches: technological development, the implementation of our already existing diagnostic methods in liquid biopsy, and the construction of well-planned disease-specifi c gene panels. Based on international trends and our experience in serum diagnostics, we are certain that liquid biopsy will become a central pillar of oncological screening and precision oncology in the near future.]

Hypertension and nephrology

DECEMBER 12, 2019

[Hypertension and brain function. Correlation of high blood pressure and demencia in aging. Hypertension in young-middle adults - demencia in elderly]

SZÉKÁCS Béla, KÉKES Ede

[The cerebral vascular damage caused by hypertension is manifested primarily in cognitive dysfunction, which is caused by hypoperfusion of brain tissue, ischemic, or bleeding stroke, or white matte injury. Hypertension may not only result in cerebral damage to the vascular background - dementia -, but may also contribute to the development and progression of classical gene-related Alzheimer’s disease. Blood pressure gradually increases in the elderly and in the very elderly, and the frequency of hypertension-mostly as isolated systolic hypertension - is 50% to 70%. High blood pressure predominately, or in full, means not only an increase in the circulatory resistance of the small children, but also, as part of the aging of the body, the rigidity (stiffness) of the arteries. At the same time, the incidence of dementia, along with age, rises sharply - up to 20% in those over 65 years of age, and over 40% in 80-90 years of age. The relationship between high blood pressure and dementia from the young age to the very old age may change as a function of current age. In the very old age of life, the varying influence of other pathological factors other than hypertension is becoming more and more important in the deterioration of both the vascular structure and the brain function. In this late stage of life, the very advanced rate of aging and nutritive blood flow often require higher perfusion pressure, and the not enough thought-out blood pressure reduction can be more damaging than a protective effect on brain condition or function. SPRINT MIND - the Intense Blood Pressure Reduction - hasn’t resolved the question, and we can legally assume that the 130-140 Hgmm SBP. Is the most favorable for dementia. The value of DBP 70 Hgmm is definitely unfavorable.]

Clinical Neuroscience

NOVEMBER 30, 2019

[Tracing trace elements in mental functions]

JANKA Zoltán

[Trace elements are found in the living organism in small (trace) amounts and are mainly essential for living functions. Essential trace elements are in humans the chromium (Cr), cobalt (Co), copper (Cu), fluorine (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn), and questionably the boron (B) and vanadium (V). According to the biopsychosocial concept, mental functions have biological underpinnings, therefore the impairment of certain neurochemical processes due to shortage of trace elements may have mental consequences. Scientific investigations indicate the putative role of trace element deficiency in psychiatric disorders such in depression (Zn, Cr, Se, Fe, Co, I), premenstrual dysphoria (Cr), schizophrenia (Zn, Se), cognitive deterioration/de­mentia (B, Zn, Fe, Mn, Co, V), mental retardation (I, Mo, Cu), binge-eating (Cr), autism (Zn, Mn, Cu, Co) and attention deficit hyperactivity disorder (Fe). At the same time, the excess quantity (chronic exposure, genetic error) of certain trace elements (Cu, Mn, Co, Cr, Fe, V) can also lead to mental disturbances (depression, anxiety, psychosis, cognitive dysfunction, insomnia). Lithium (Li), being efficacious in the treatment of bipolar mood disorder, is not declared officially as a trace element. Due to nutrition (drinking water, food) the serum Li level is about a thousand times less than that used in therapy. However, Li level in the red cells is lower as the membrane sodium-Li countertransport results in a Li efflux. Nevertheless, the possibility that Li is a trace element has emerged as studies indicate its potential efficacy in such a low concentration, since certain geographic regions show an inverse correlation between the Li level of drinking water and the suicide rate in that area. ]