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Clinical Neuroscience

SEPTEMBER 30, 2020

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.

Lege Artis Medicinae

SEPTEMBER 30, 2020

[Thyroid disease – essentials for the everyday practice]

BAKOS Bence, TAKÁCS István

[Thyroid disorders are very frequent not only among endocrine diseases but also the general conditions. Every clinician, regardless of their specialty, meet patients with thyroid disorders during their everyday practice. While diagnostic and therapeutic options remained almost unchanged in the past decade, there are several inten­sively researched topics in the patient’s care, advances of which we ought to familiarize ourselves with. In this present paper we sought out to cover three of these fiercly discussed topics. ]

Lege Artis Medicinae

JULY 01, 2020

[Persisting Hashimoto’s thyroiditis converting to Graves’ disease]

TÓTH Géza

[Graves’disease and Hashimoto’s thyroiditis are the two most important types of autoimmune thyroid dis­eases. Autoimmune hyperthyroidism commonly leads later on to hypothyroidism. The conversion from persisting Hashimoto-thyroiditis to hyperthyroidism is rare in the literature. The author presents the cases of two patients, whose Hashimoto’s thyroiditis treated with thyroxin for years, changed into Graves’ hyperthyroidism sponta­neously. CASE REPORT – The patients had been diagnosed with autoimmune hypothyroidism since several years. The clinical symp­­toms, the low peripheral hormone le­vels, the high level of antithyroid antibo­dies and the ultrasound imaging confirmed the hypertrophic form of Hashimoto’s thy­roiditis. After several years of high dose le­vothyroxin treatment, clinical symptoms of hyperthyroidism have appeared. After omit­ting the substitution, the thyroid hormone levelled off at high values and the level of anti-TSH receptor antibodies raised too. The diffuse, obviously increased blood flow of the thyroid glands, and in one of the patients the thyroid scan, confirmed the Graves’ disease. During the thyreostatic treatment, the symptoms of the patients disappeared, they became euthyreoid and the antibody levels decreased as well. The Graves’ disease and the Hashimoto’s thyroiditis have many common features. These immunological, ge­netic and other common features enable the mutual transition of these two diseases.]

Clinical Neuroscience

MAY 30, 2020

[The long-term follow-up of enzyme replacement treatment in late onset Pompe disease]

MOLNÁR Mária Judit, BORSOS Beáta, VÁRDI Visy Katalin, GROSZ Zoltán, SEBÕK Ágnes, DÉZSI Lívia, ALMÁSSY Zsuzsanna, KERÉNYI Levente, JOBBÁGY Zita, JÁVOR László, BIDLÓ Judit

[Pompe disease (PD) is a rare lysosomal disease caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme due to mutations in the GAA gene. The enzymatic deficiency leads to the accumulation of glycogen within the lysosomes. Clinically, the disease has been classically classified in infantile and childhood/adult forms. Presently cc. close to 600 mutations distributed throughout the whole gene have been reported. The c.-32-13T>G splice mutation that is very common in patients of Caucasian origin affected by the childhood/adult form of the disease, with an allelic frequency close to 70%. Enzyme replacement treatment (ERT) is available for the patients with Pompe disease (Myozyme). In this paper, we are presenting the long term follow up of 13 adult onset cases treated more than 5 years. The longest follow up was 15 years. To evaluate the treatment efficacy, the 6 minutes walking test (6MWT) and the respiratory functions were monitored annually. The analysis revealed that at the beginning of ERT for 3-4 years the 6MWT had been generally increasing, then it declined, and after 10 years it was lower in 77% of the cases than it had been at the start of the treatment. In 23% of the cases the 6MWT increased during the follow up time. Only one of the patients become wheelchair dependent during the follow-up period. The respiratory function showed similar results especially in supine position. A high degree of variability was observed among patients in their responses to the treatment, which only partially associated with the antibody titer against the therapeutic protein. The efficacy of the ERT was associated with the type of the disease causing mutation, the baseline status of the disease, the lifestyle and the diet of the patient. The long-term follow up of the patients with innovative orphan drugs is necessary to really understand the value of the treatment and the need of the patients.]

Clinical Oncology

APRIL 10, 2019

[CDK 4/6 Inhibitors in Breast Cancer: Current Controversies and Future Directions]

SPRING M. Laura, WANDER A. Seth, ZANGARDI Mark, BARDIA Aditya

[Purpose of review: To describe the clinical role of CDK 4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer (HR+MBC) as well as current controversies and evolving areas of research. Recent fi ndings: Palbociclib, ribociclib, and abemaciclib are each approved in combination with an aromatase inhibitor or fulvestrant for HR+MBC. Abemaciclib is also approved as monotherapy for pre-treated patients. Key questions in the fi eld include whether all patients with HR+MBC should receive a CDK 4/6 inhibitor up front versus later line, impact on overall survival, role of continued CDK 4/6 blockade, mechanism of clinical resistance, and treatment sequencing. Summary: The development of CDK 4/6 inhibitors has changed the therapeutic management of HR+MBC. Additional research is needed to determine optimal treatment sequencing, understand mechanisms governing resistance, and develop novel therapeutic strategies to circumvent or overcome clinical resistance and further improve the outcomes of patients with MBC.]

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. ]

Lege Artis Medicinae

MAY 20, 2019

[Perinatal faulty hormonal imprinting: early impact, late consequences]

CSABA György

[The description and basic study of hormonal imprinting were the first in the series of research, which led to the recognition of the role of perinatal chemical effects in the late (adult age) manifestation of some diseases and inclination to diseases. Today it is clear, that certain pathological states, as obesity or diabetes, hypo- or hyperactivity (autoimmunity and allergy) of immune system can be deduced to perinatal (hormonal or metabolic) imprinting. The perinatal hormonal (chemical) imprinting takes place at the first encounter between the developing hormone receptor and the target hormone which sets the binding capacity of the receptor for life. In the critical periods of ontogeny (in addition to the perinatal imprinting) it can be developed at weaning, in adolescence and in continuously dividing and differentiating cells during the whole life. It is provoked by considerable quantitative differences of the physiological hormone or the presence of strange target-hormone-like molecules. The faulty hormonal imprinting leads to the adult-age diseases at any time of life and is inherited epigenetically to the progeny generations. Faulty hormonal imprinting always could be present in earlier times however, at present, because of the erroneous multiplication of endocrine disruptors in the environment, nutrition and medicine, its importance is continuously growing. The effects of faulty hormonal imprinting seem to be dangerous however, it can be imagined in the far future also a positive effect by the transformation of the human endocrine system at an evolutionary route. In the metabolic or immunological imprinting as well, as in the DOHaD (Developmental Origins of Health and Disease) the foremost recognized hormonal (chemical) imprinting is materialized.]

Lege Artis Medicinae

DECEMBER 10, 2018

[Experimental investigation of the complex energy balance]

GARAMI András

[The complex energy balance includes maintenance of both normal body mass and body temperature. In the homeostasis regulation it is important that the activities of several physiologic processes are balanced with each other, for example, the balance between food intake and energy expenditure is crucial to maintain normal body mass, while the balance between heat production and heat loss is vital in determining body temperature. Obesity and loss of body weight, as well as fever and hypothermia are consequences of the dysregulation in energy balance. In our research, we studied receptorial and neurohumoral mechanisms involved in the maintenance and in the impairment of energy balance. This paper gives an overview of our most important findings, which served as the basis of the application submitted to and awarded with 3rd prize by the Prof. Dr. Laszlo Romics Memorial Foundation. We review the physiologic role of transient receptor potential channels, mostly of vanilloid-1 (formerly: capsaicin receptor) in the regulation of body temperature and body mass. Among the neuropeptides which take part in the maintenance of energy balance, we present the thermoregulatory effects of alpha-melanocyte stimulating hormone and pituitary adenylate cyclase-activating polypeptide. Last, among the molecular mechanisms of systemic inflammation, which is characterized by thermoregulation disorders (e.g., fever, hypothermia), we recap the role of the vanilloid-1 and neurokinin-1 receptor, and bilirubin.]

Clinical Neuroscience

NOVEMBER 30, 2018

Inflammatory biomarkers in benign paroxysmal positional vertigo: A Turkey case-control study

AYSEL Tekeşin, ABDULKADIR Tunç

Objective - Benign paroxysmal positional vertigo (BPPV) is the most common cause of recurrent vertigo. Inflammation is a hypothetic etiological factor in BPPV. The aim of this study was to evaluate inflammatory biomarker levels in BPPV patients and compare these with the healthy subjects. Materials and methods - This prospective case-control study was conducted with 114 newly diagnosed BPPV patients and age- and sex- matched 83 healthy subjects. The laboratory investigations included serum hemogram, full biochemistry profiles, vitamin levels, thyroid hormone profiles, high sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR). Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte to HDL-cholesterol ratio (MHR) values were calculated and compared between the patients and healthy subjects. Results - The mean age was 39.1 ± 12.4 years for patients, and 37.0 ± 11.9 for controls. Vitamin B12, hematocrit (Hct), creatinine, urea, and fT4 values, lymphocyte, total bilirubin, direct bilirubin and indirect bilirubin levels were significantly lower in BPPV patients (p ˂ 0.05), while HDL, SGOT, and ESR values were significantly higher. In the BPPV patients the mean NLR, PLR, and mean platelet volume (MPV) values were significantly higher than in the control subjects. Neutrophil, platelet, monocyte, MHR, and CRP values were similar in both groups (p ˃ 0.05). Conclusion - Our result suggests that NLR, PLR, MPV, ESR, and bilirubin levels should be taken into account as potential biomarkers of BPPV. As they are inexpensive parameters and widely available, they can be used in clinical practice for prediction of BPPV. However, further large-scale studies are required to confirm this relationship.

Journal of Nursing Theory and Practice

JUNE 30, 2018

[The effect of sensory deficit induced by anterior crutiate ligament injury on postural control]

NOVÁK Szabina, NAGY Edit

[The balance parameters and the loading symmetry was assessed in a subject with anterior cruciate ligament deficiency. A 14 days intensive training was performed mainly with eyes closed in closed kinematic chain exercises, loading the affected limb. Stabilometry and the assessment of loading symmetry was performed. The sway path was calculated in two direction. The sway path comparisons did not revealed significant differences only a tendency of decrease in anteroposterior direction. Interestingly we found an increased loading of the affected limb after our intensive training, with a mismatch between the subjective perceived symmetry and the objective symmetry data. The changed symmetry perception might be explained with the change in proprioceptive information processing induced by the training. In the future further examinations with higher case number are necessary to support this result. ]