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Clinical Oncology

APRIL 30, 2020

[Biological clock and cancer]

VELLAINÉ Takács Krisztina, SZTANKOVICS Dániel, HOFFMANN Gyula, KOPPER László, GÁLOSI Rita

[In the present paper, we are giving a review about the circadian rhythm of the biological rhythm, its regulation and relation to tumorigenesis. The circadian rhythm is an approximately 24-hour cycle in biochemical, physiological processes in organisms from unicellular to vertebrates. This biological rhythm is generated by the synchronization of our endogenous clocks and the light as the main “Zeitgeber”. The nucleus suprachiasmaticus (SCN) of the hypothalamus is the region, which is considered to be the circadian “main clock” of the organism and is responsible for coordinating peripheral clocks in different organ systems. At the cellular level, the regulation of the circadian rhythm is basically provided by the so-called “circadian locomotor output cycles kaput” the CLOCK genes. The discovery of those cellular mechanisms was awarded with Nobel Prize in 2017. The CLOCK genes, acting on other effector genes, regulate diurnal rhythm of protein synthesis. More and more data are available, which suggest that there is an association between circadian genes and tumor development. Furthermore, many studies show a link between the shift work and the development of breast and prostate cancer and between mutations in some circadian genes and development of carcinomas. More data suggest a relationship between tumor metabolism and CLOCK genes and their regulations. Based on all these data, the circadian rhythm, so the time of day, may need to be taken into account during cancer therapy.]

Clinical Neuroscience

NOVEMBER 20, 2015

[Hyperglycaemic hemiballismus: implications from connectivity analysis for cognitive impairments]

KINCSES Tamás Zsigmond, VADÁSZ Dávid, NÉMETH Dezsõ, JANACSEK Karolina, SZABÓ Nikoletta, DÉZSI Lívia, BABOS Magor, VÖRÖS Erika, VÉCSEI László

[Hyperglycaemia induced movement disorders, such as hemiballism are rare disorders. The syndrome is characterised by the triad of hemiballism, contralateral T1-hyperintense striatal lesion and non-ketotic hyperglycaemia. Here we report a patient with untreated diabetes presenting with acute onset of hemiballism. MRI revealed T1 hyperintensity of the head of the caudate nucleus and the anterior putamen. The patient also had acantocytosis. Based on the detailed examination of the neuroradiological results and earlier findings we will imply on the pathomechanism. Based on previous findings microhemorrhages, extensive mineralisation, gemistocytic astrocytosis might play role in the development of the imaging signs. The connectivity pattern of the striatal lesion showed extensive connections to the frontal cortex. In coexistence with that the most severe impairment was found on the phonemic verbal fluency task measuring frontal executive functions. ]

Clinical Neuroscience

JANUARY 30, 2016

Facial virus inoculations infect vestibular and auditory neurons in rats

HELFFERICH Frigyes, LOURMET Guillaume, SZABÓ Rebeka Éva, BOLDOGKŐI Zsolt, PALKOVITS Miklós

Background and purpose – There is growing evidence for the viral origin of the Bell’s facial palsy, vestibular neuritis and sudden sensorineural hearing loss, however their exact pathophysiology is still unknown. We investigated the possibility of brainstem infections following peripheral viral inoculations in rats. Methods – Pseudorabies virus, a commonly used neurotropic viral retrograde tracer was injected into the nasolabial region of rats. Five and 6 days after injections, infected brainstem nuclei were demonstrated by immunohistochemical techniques. Results – Infected neurons were found in the motor facial, the medial vestibular, and the sensory trigeminal nuclei, as well as in the medial nucleus of the trapezoid body. Conclusion – Pseudorabies virus infects auditory and vestibular sensory neurons in the brainstem through facial inoculation. The possible routes of infections: 1. trans-synaptic spread constituted by facio-vestibular anastomoses: primarily infected motor facial neuron infects neurons in the medial vestibular nucleus, 2. via trigeminal sensory nerves: the sensory trigeminal complex innervated by GABAergic medial vestibular neurons, and 3. one bisynaptical route: infected facial motoneurons may receive indirect input from the medial vestibular nucleus and the trapezoid body via connecting neurons in the sensory trigeminal complex. We may assume that latent infections of these areas may precede the infections of the peripheral organs and the reactivation of the virus exerts the symptoms.

Clinical Oncology

MAY 10, 2018

[Fusions in solid tumors]

KOPPER László

[Genetic fusions are the cosequence of genomic rearrangement including chromosomal inversion, interstitial deletion, duplication, amplifi cation, translocation. Fusions can influence tumor development and progression. Fusions fi rst discovered in hematological malignances (e.g. BCR-ABL), butlater more and more were identified dueto the higly sensitive NGS. It has been found that the oncogenic fusions are in minority in a given tumor. Today, some fusions were apprevedas targets (ALK, ROS1, PDGFB) by FDA. Asino ther targeted therapy resistance is in evitable, which is a very important challenge for newly designed drugs.]

Clinical Neuroscience

NOVEMBER 30, 2018

[Comparison of subthalamic nucleus planning coordinates in 1Tesla and 3Tesla MRI for deep brain stimulation targeting ]

JUHÁSZ Annamária, KOVÁCS Norbert, PERLAKI Gábor, BÜKI András, KOMOLY Sámuel, KÖVÉR Ferenc, BALÁS István

[Backgroud - Deep brain stimulation (DBS) involves placing electrodes within specific deep brain nuclei. For movement disorders the most common indications are tremors, Parkinsons disease and dystonias. Surgeons mostly employ MR imaging for preoperative target selection. MR field geometrical distortion may contribute to target-selection error in the MR scan which can contribute to error in electrode placement. Methods - In this paper we compared the STN target planning coordinates in six parkinsonian DBS patients. Each patient underwent target planning in 1T and 3T MRI. We statistically compared and analysed the target-, and the fiducial coordinates in two different magnetic fileds. Results - The target coordinates showed no significant differences (Mann-Whitney test, p > 0.05), however we found significant difference in fiducial coordinates (p < 0.01), in 3T MRI it was more pronounced (mean ± SD: 0.8 ± 0.3 mm) comparing to 1T (mean ± SD: 0.4 ± 0.2 mm). Conclusion - Preliminary results showed no significant differences in planning of target coordinates comparing 1T to 3T magnetic fields.]

Lege Artis Medicinae

SEPTEMBER 20, 2018

[Multidisciplinarity and pulmonary hypertension in idiopathic pulmonary fibrosis]

BOHÁCS Anikó, KARLÓCAI Kristóf, KERPEL-FRONIUS Anna

[Idiopathic pulmonary fibrosis (IPF) is a subgroup of the fibrotising idiopathic interstitial pneumonias occuring primarily in older adults. It is characterised by progressive decline of lung function and is associated with high mortality. IPF is frequently associated with pulmonary hypertension (PH). PH has unfavourable impact on the prognosis of IPF. PH should be suspected in IPF patients presenting with dyspnoe, desaturation on exertion and disproportionately low diffusion capacity. Transthoracic echocardiography is used to screen for PH in IPF patients. Although right heart catheterization is the gold standard procedure for the diagnosis of PH, this is not regularly performed on IPF patients. Chest high resolution computer tomography (HRCT) is essential for the diagnosis of IPF. IPF is typically characterised by the presence of usual interstitial pneumonia (UIP) pattern on HRCT. Multidisciplinary discussion bet­ween experienced pulmonologists, radiologists, and pathologists is key in the early and accurate diagnosis of IPF. An important role of the interstitial lung disease-multidisciplinary team (ILD-MDT) is to determine whether other diagnostic examinations and surgical lung biopsy is needed, in an attempt to reduce unnecessary risk. ILD-MDT should propose the initiation of antifibrotic therapies that have the potential to reduce disease progression. All patients diagnosed with IPF, with no contraindications for lung transplantation, should be referred early to a transplant committee.]

Lege Artis Medicinae

AUGUST 30, 2018

[How to diagnose idiopathic pulmonary fibrosis. Part 2]

HORVÁTH Ildikó, KERPEL-FRONIUS Anna, HARKÓ Tünde

[Idiopathic pulmonary fibrosis is a severe irreversible lung disease with a progressive course. The disease onset is hard to discover due to the unspecific signs and symp­toms. It occurs mainly in elderly people. In the past decades its prevalence has increased continuously. Physical examination, restrictive pattern on lung function test with decreased diffusion capacity are characteristic features of the disease. Chest X-ray showing fibrotic pattern also points toward the diagnosis of idiopathic pulmonary fibrosis. Differential diagnosis is based on high resolution komputertomográfy. Diag­nosis of IPF is based on the appearance of usual interstitial pneumonia pattern together with the lack of external risk factors and autoimmune or other diseases also known to cause this pattern seen on chest imaging. If no firm diagnosis can be built lung biopsy is required. Multidis­ciplinary teams from clinician, radiologist and pathologist are set in predefined centres that could provide care with novel antifibrotic drugs. These can slow disease progression and are in the frontline in the treatment of the disease. Further research is required to understand the pathomechanism and foster the discovery of further treatment options. ]

Lege Artis Medicinae

JUNE 20, 2018

[Diagnosis of interstitial lung diseases]

MÜLLER Veronika

[Recognition and diagnosis of interstitial lung diseases (ILD) is one of the most challenging tasks of respiratory medicine. In the wide range of different ILD-s idiopathic pulmonary fibrosis (IPF) is one of the most common. Improvements in the diagnosis made the recognition of IPF easier. Typical clinical features and usual interstitial pneumonia pattern on high resolution CT are now enough for the confident diagnosis of IPF in the multidisciplinary ILD-team discussions. Bronchoscopic cryobiopsy is a great achievement of histological sampling as this can give appropriate size tissue for histological analysis making surgical intervention rare. As IPF cannot be cured early diagnosis is crucial. Today available treatments can only slow down progression of the disease, so early stages and better clinical condition of the patients are essential for therapeutic success. Follow-up of IPF patients includes complex lung functional measurements in dedicated centers in Hungary. Former studies confirmed forced vital capacity (FVC) decline as an important measure of disease progression and mortality. Available IPF treatments decrease FVC decline and can prevent the mostly deadly acute exacerbations of the disease. Additionally palliative treatments including supplementary oxygen and in selected patients lung transplantation can be offered. This is the first of a series of three articles about IPF. ]

Clinical Oncology

MAY 10, 2017

[Pneumonitis - severe adverse effect of therapy]

VÁRNAI Zsuzsanna

[The interstitial lung diseases (ILD) are a heterogeneous group of disorders that are classifi ed together because of similar clinical, radiographic or pathologic manifestation. The diffuse interstitial lung diseases are divided into those that are associated with known causes and that are idiopathic. The treatment choices and prognosis vary among the different causes and types of ILD, so the early and correct diagnosis is important. In oncology ILD could be a rather severe adverse effect of treatment with radiationor chemotherapy.]

Hypertension and nephrology

SEPTEMBER 10, 2016

[Hypertension and left ventricular hypertrophy]

MATOLTSY András

[Left ventricular hypertrophy (LVH) is defined as an increase in the mass of the left ventricle. In addition to the absolute increase in mass, the geometric pattern of LVH also may be important. LVH can be secondary to an increase in wall thickness, an increase in cavity size, or both. LVH as a consequence of hypertension usually presents with an increase in wall thickness. This increase in mass predominantly results from a chronic increase in afterload of LV caused by the hypertension, although there is also a genetic component. A significant increase in the number and/or size of sarcomeres is the main pathologic mechanism, but hypertension may also result in interstitial fibrosis. The estimation of mass is commonly derived from measurements obtained by echocardiography. LVH is associated with increased incidence of systolic and/or diastolic dysfunction, heart failure, myocardial infarction, ventricular arrhythmias, sudden cardiac death, aortic root dilatation, and a cerebrovascular event. The cardiovascular risk is directly related to the degree of mass. The regression of LVH is associated with a reduction in cardiovascular risk and improved cardiac function. Regression of LVH is associated with weight loss, dietary sodium restriction, and use of ACE inhibitors, ARBs, some calcium channel blockers, and some sympatholytic agents.]