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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.

Hypertension and nephrology

SEPTEMBER 12, 2018

[Treatment of hypertension in kidney transplant patients]

KOVÁCS Tibor, WAGNER László

[Most of the renal transplant recipients suffer from hypertension. Hypertension substantially contributes to the high cardiovascular mortality in this population. The recommendation of the Hungarian Society of Hypertension and the international guidelines suggest to achieve less than 130/80 mmHg as target blood pressure in these patients. Several factors may be in the background of hypertension after kidney transplantation, which can be summarized as factors from the recipient-side, the donorside and factors provoked by transplantation itself. In most of the cases early after transplantation high doses of immunosuppressive drugs (especially calcineurin inhibitors and steroids) are responsible for the increased blood pressure. There are some further special methods apart from the general recommendations which are needed during the examination of hypertension of kidney transplant patients: e.g. measurement of blood trough-level of immunosuppressive drugs, investigation of bone-mineral disorder, screening for the level and causes of anaemia, check-up of the renal graft circulation. Kidney transplant patients suffering from hypertension usually need more than two antihypertensive drugs beyond the use of non-pharmaceutical antihypertensive methods. In the early posttransplantation period calcium channel blockers are preferred antihypertensive medications, because they counterbalance the vasoconstrictive effect of calcineurin inhibitors. The administration of renin-angiotensin-aldosterone inhibitors are rather suggested after the stabilization of renal function (from the 1-3 months posttransplantation). When designing antihypertensive strategy, comorbidities and special factors should be regarded as well, especially volume overload, proteinuria, allograft function (GFR), diabetes, other cardiovascular risk factors, previous cardiovascular events. The setup of an individual therapeutical strategy is advised in view of all these factors, which is different according to the timing after transplantation: the perioperative, the early postoperative phases and from 1-3 months after transplantation have special focuses.]

Clinical Neuroscience

SEPTEMBER 20, 1996

[Prognosis of neuroepithelial tumours by means of cell proliferation studies]

GYÖMÖRI Éva, MÉSZÁROS István, MÉHES Gábor, DÓCZI Tamás, PAJOR László

[Cell-kinetic analysis of tumours has recently been widely used in clinical oncology for prognosis of patients treated with malignant neoplasms and for controlling the efficiency of treatment protocols. Definition of biological nature of neuroepithelial tumours was based on grading depending on the severity of cellular anaplasia. Neuroepithelial tumours can be characterized not only by the histological features but also by the DNA content and abnormalities of the cell proliferation – though the relationship between histological malignancy, proliferative activity and cellular aneuploidity was found to be rather controversial according to the literature. In this review article the clinical value of cell cycle analysis such as distribution of DNA content, DNA index; S-phase fraction; proliferation-markers [MIB 1 antibody, bromdeoxy uridin labelling index, mitotic index, definition of nucleolar organization region) are discussed on the basis of personal experience and review of the appropriate literature. Flow cytometry and examination of proliferation markers have a significant role in the definition of prognosis of patients suffering from WHO grade II and III neuroepithelial tumours. Gliomas giving rise to recidivism have a rapid cell cycle already at their first occurrence, which is characterized by raised proliferation indices, and occurrence of aneuploid cell clones. An unfavourable outcome can be prognosed in patients suffering from a WHO grade II or III glioma if the DNA index is above or below 1+0.1 if the value of the S phase fraction is above 6%, if more than 1 mitosis is found in 10 large magnification field, and if the number of cells labelled with MIB 1 antibody exceeds 3 in 1 large magnification field. The literature confirms our notion that further studies of proliferation characteristics may help in the production of a malignity score of gliomas that could support the efficiency of traditional histological grading in prognosis and control of complex therapy of these tumours.]

Hypertension and nephrology

APRIL 29, 2021

[Case report of supine hypertension and extreme reverse dipping phenomenon decades after kidney transplantation]

BATTA Dóra, KŐRÖSI Zita Beáta, NEMCSIK János

[Supine hypertension, a consequence of autonomic neuropathy, is a rarely recognized pathological condition. Reported diseases in the background are pure autonomic failure, multiple system atrophy, Parkinson’s disease, diabetes and different autoimmune disorders. In our case report we present a case of supine hypertension which developed in a patient decades after kidney transplantation. The patient was followed for 25 months and we demonstrate the effect of the modification of antihypertensive medications. At the time of the diagnosis supine hypertension appeared immediately after laying down (office sitting blood pressure (BP): 143/101 mmHg; office supine BP: 171/113 mmHg) and on ambulatory blood pressure monitoring (ABPM) extreme reverse dipping was registered (daytime BP: 130/86 mmHg, nighttime BP: 175/114 mmHg). After the modification of the antihypertensive medications in multiple times, both office supine BP (office sitting BP: 127/92 mmHg; office supine BP: 138/100 mmHg) and on ABPM nighttime BP improved markedly (daytime BP: 135/92 mmHg, nighttime BP: 134/90 mmHg). In conclusions, our case report points out that autonomic neuropathy-caused supine hypertension and extreme reverse dipping can develop in chronic kidney disease, after kidney transplantation. The modification of the antihypertensive medications can slowly restore this pathological condition.]

Journal of Nursing Theory and Practice

DECEMBER 30, 2018

[Judgement of organ donations’ nursing-related problems by nurses in the light of a Hungarian survey ]

SZÉCSÉNYI Péter, RAJKI Veronika

[Aim of the study: The research aims to map the opinions of nurses working on transplantation wards about the preparedness of laic people in relation to the theme of organ donation. In addition, we wanted to examine whether nurses give preference to religious beliefs and ethical principles against legal regulation. We also wondered whether nurses working on transplantation wards would offer their own organs. Materials and methods: The descriptive study was conducted among transplant nurses in Budapest, Szeged and Pécs, using a self-constructed questionnaire. Our results were obtained using a Pearson’s Chi-square test (all statistically significant levels were set at P<0.05), as well as using the one sample t-test. Results: The total sample size was 37. According to nurses, the laic population does not have the sufficient knowledge about the current legal rules. Nurses are positively committed to offering their own organs for a possible donation. In relation to organ donation, nurses prefer the religious and ethical principles against legal rules. Conclusions: The laic population is not fully aware of organ donation, which puts the success of organ donation at risk. It would worth to involve transplant nurses into the education of the laic population to improve the general acceptance of organ donation who work in transplantation fields and who do donor care, so laics would be more accepting and less conflict would occur, supposedly more organ transplants would occur.]

Lege Artis Medicinae

OCTOBER 20, 2018

[Gene modified T cells against cancer]

SZÖŐR Árpád

[Chimeric antigen receptor modified (CAR) T cells are hailed as a revolutionary breakthrough in the field of oncology. CAR T cells were first applied, with outstanding success, in the treatment of various leukaemias, yielding unprecedented antitumor activity and long periods of disease free survival. Following the success of CAR T cell therapy in leukaemias, solid tumors should now be targeted. These are more complex targets, therefore CAR T cell therapy needs to be further optimized for this purpose. Also, some unfortunate side effects, including the potentially deadly global inflammation called cytokine storm have to be minimized and possibly even eradicated. The next decade will be an exciting time to define whether this therapy which is yet exclusively used for cancer patients is also successful in the treatment of other diseases. In a recent study, T cells reengineered with CAR derived chimeric autoantibody receptors (CAAR) efficiently prevented disease progression in pre-clinical animal models simulating the serious autoimmune disorder, pemphigus vulgaris. Therapy was based on CAAR constructs which have the unique ability to selectively recognize and eliminate the B-cell clones secreting autoantibodies against a self-protein, thus playing a key role in disease pathogenesis and progression. In this review, we would like to give an overview about the history of the CAR T-cell concept, summarize briefly the currently running clinical trials, and discuss the challenges and future prospects of CAR T-cell therapy.]

Lege Artis Medicinae

SEPTEMBER 30, 2020

[Frequency and risk factors of “de novo” tumors after kidney transplantation ]

BORDA Bernadett, HÓDI Zoltán, SZEDERKÉNYI Edit, OTTLAKÁN Aurél, SEREGÉLY Edit, LÁZÁR György, KERESZTES Csilla, VIRÁG Katalin

[After kidney transplantation, the administration of immunosuppressive therapy not only renders the patient susceptible to infections, but it may also damage the function of tumor cell recognition and elimination. Our study was performed at the Department of Surgery, University of Szeged. After establishing the inclusion criteria, 570 patients were involved in the study. We examined the age, sex, immunosuppressive therapy of the patients, and searched for the rela­tionship between the different immunosuppressive agents and the type of the tumor. In 81 cases, de novo cancer was diagnosed. Among patients treated with cyclosporin and tacrolimus there was no significant difference in the mean age (p = 0.734) and body mass index (p = 0.543). There was no significant difference in graft function between the two groups of patients (Tac vs Cyc; 44 vs 20). Related to the time passed since the trans­plantation to diagnosing the tumors the earliest were prostate and cervix cancers however without significant difference. Skin cancers are the most frequent followed by post-transplant lym­pho­prolife­ra­tive diseases. The increasing risk of developing tumors is mainly due to immunosuppressive therapy. ]

Clinical Oncology

DECEMBER 30, 2019

[Cell death]

KOPPER László, TÍMÁR József

[Cell proliferation and cell death (mainly apoptosis) have programs forming a network to maintain the functional integrity of the organism. Apoptosis has an external and internal units with ligands, signalling pathways and targets. Besides, some other participants (e.g. p53) are involved in the regulation of cell death. Although, apoptosis is a multitargeted process, there is no useful therapy, if it is needed, to correct accumulation of unwanted cells.]

Clinical Neuroscience

SEPTEMBER 30, 2020

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Lege Artis Medicinae

MAY 20, 2019

[Immuno-oncology therapy in patients with non-small cell lung cancer]

CSÁNKY Eszter

[Despite decades of smoking cessation programs, and lung cancer screening programs, mortality due to bronchial cancer leads the mortality statistics among cancer deaths worldwide. Platinum-based chemotherapy has not fundamentally altered the effectiveness of treating non-small cell lung cancer (NSCLC). One of the newest approaches to the use of immunotherapeutic treatments in recent years is the so-called. use of immune checkpoint blocking agents. PD-1 and PD-L1 blockers of this type have been subjected to a large number of clinical trials in lung cancer and were reported by the tumor III.b / IV. stage. Last year, in 2018, we again came up with a milestone in the treatment of lung cancer immuno-oncology, as compared to the previous stage, III.a / III.b Durvalumab con­solidation therapy for non-small cell lung cancer after inoperative, non-chemo-radiotherapy phase I, is based on the results of the PACIFIC clinical trial. PACIFIC was a triple-phase, randomized, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of durvalumab consolidation therapy, irresistible, III. patients with non-small cell lung carcinoma who have not progressed after platinum-based chemo-radiotherapy. The PD-L1 expression level of the tumor was not an admission criterion. In the study, 713 patients were randomized to durvalumab and placebo for 2:1, progression-free survival (PFS) and over­all survival (OS) as their primary endpoint. Summarizing the results of the study, durvalumab provided significant benefit to patients at both endpoints. PFS and OS values were also significantly longer for durvalumab than placebo, and the safety profile of durvalumab was consistent with previous PD-1, PD-L1 inhibition tests.]