Hypertension and nephrology

[The 19th Debrecen Nephrology Days 26-29 May 2014]

REUSZ György

SEPTEMBER 20, 2014

Hypertension and nephrology - 2014;18(03-04)

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Hypertension and nephrology

[Serum uric acid in primary hypertension: cause or consequence? - Data from SEPHAR II Survey]

DOROBANTU Maria, TAUTU Oana-Florentina, BUZAS Roxana, LIGHEZAN Daniel

[Objectives: To evaluate a possible link between serum uric acid (SUA) levels, arterial stiffness and atherogenic index of plasma on one hand and renal function on the other and to test the role of SUA in the assessment of total cardiovascular risk. Materials and methods: We studied serum uric acid levels (SUA) in 1975 subjects included in SEPHAR II survey. We measured arterial stiffness parameters, calculated atherogenic index of plasma and estimated glomerular filtration rate (eGFR) by MDRD and CKD-EPI formulae and assessed total cardiovascular risk according to current ESH-ESC risk stratification chart. Results: The highest SUA values were recorded in subjects with grade III HT and were correlated with increased arterial stiffness and with increased atherogenic index of plasma. The lowest eGRF values, assessed by both MDRD and CKD-EPI, were observed among subjects with hyperuricemia and a significant indirect correlation between SUA and eGFR was evidenced. A proportional correlation between SUA values and total CV risk was also obtained. Conclusions: The study supports SUA implication in the pathogenesis of elevated blood pressure and the role of uric acid as a cardiovascular risk factor, particularly for the development of hypertension and renal disease.]

Hypertension and nephrology

[The measurement of blood pressure variability with „visit-to-visit” method in the OPAL study]

KÉKES Ede, KISS István

[Authors reanalysed the 2 years-data of OPAL study for evaluation of change in blood pressure variability. The visit-to-visit form of long term measurement method was selected for characterization of the variability. The decrease of blood pressure fluctuation due to antihypertensive treatment was measured with the standard deviation of mean values and the variation koefficient. According to our observation the combined ACE inhibitor + amlodipine therapy was effective not only in the respect of systolic and diastolic target pressure, but - with continuous reduction - the BPV indices reached the level of normotensive subjects in the end of first year of treatment.]

Hypertension and nephrology

[Visualization of glomerular filtration in animals in vivo - significant filtration in afferent arteriola. Regulation of endothelial permeability]

ROSIVALL László

[Recently we have in vivo visualized glomerular filtration and fluid flow from the JGA portion of afferent arteriole into JGA using intravital multiphoton microscopy. Fluorescence of the extracellular fluid marker lucifer yellow appeared in the interstitium around the distal portion of afferent arteriole before the filtration into Bowman's capsule. In isolated microperfused JGA we demonstrated fluid movement from the glomerulus into the MD tubule. All these prove that there is a significant and dynamic fluid flow exists in the JGA. Angiotensin II similar to VEGF plays a role in regulation of permeability/fenestration formation. Angiotensin II acts through AT1 receptor and PV-1 protein synthesis.]

Hypertension and nephrology

[Changes in prescribing practice of diuretics in the treatment of hypertension between 2007 and 2013 in the mirror of insurance data]

BARNA István, GYURCSÁNYI András

[Amongst diuretics, thiazides are the most commonly used antihypertensive agents. Due to their long-term effect, they are ideal for treatment of hypertension. Indapamide is a long-acting (half-life 14-16 hours) thiazide-like diuretic, which is effective in very small doses (1.25 to 5 mg). Indapamide mainly provides a forceful blood pressure lowering effect, by decreasing arteriolar and peripheral resistance due to its vasodilatative effect. Even in hypertensive, diabetic patients, indapamide does not affect the lipid metabolism or the carbohydrate metabolism. As an antihypertensive medicine, thiazide-type diuretics (only in small doses - 6.25- 12.5 mg hypothiazide, 12.5 mg chlorthalidone, 5 mg clopamide) can be the first choice, when dealing with essential hypertension disease without complications. They may also be used in monotherapy. When dealing with hypertension associated with old age or with isolated systolic hypertension, these products are recommended with “A” type evidence. For the treatment of left ventricular hypertrophy and post-stroke conditions associated with the treatment of hypertension, it is recommended to use indapamide in case of diabetes, furosemide and thiazide in case of a left ventricular dysfunction and heart failure, or a combination of these. When reviewing the national sales of mono-component diuretics between 2007 and 2013 in the National Health Insurance (OEP) database, we could see that the sales of hydrochlorothiazide, clopamide, and chlorthalidone decreased. In 2013 however, the sales of the latter experienced a turnover, which might indicate the activity of the followers of the new guideline. The use of diuretics with indapamide as their active substance increased. The prescription of diuretics used in a combination increased continuously between 2007 and 2010 and reached a monthly one million prescribed boxes. During the time in question, the use of products combined with hydrochlorothiazide (most products contain this agent) was the most dominant, but its share fell from 88% to 66% due to the growth of combinations containing the active ingredient indapamide. This is interesting because this combination is “unique” (perindopril + indapamide). During the period in question, only the prescription of this combination increased steadily. The use of diuretics is very important in antihypertensive therapy. If we compare the diuretics and their combinations to the recommendations, we can state that the treatment is done along the guidelines, or in other words the use of the metabolic neutral combination therapy is increasing.]

Hypertension and nephrology

[Local importance of Hantavirus infections in mirror of the latest virological, epidemiological and clinical results]

NÉMETH Viktória, OLDAL Miklós, SEBÕK Judit, WITTMANN István, JAKAB Ferenc

[Hantaviruses are widespread infectious agents carried by different rodent species. The majority of them belongs to viral zoonotic pathogens, sometimes causing severe human infections. Hantaviruses inflict hemorrhagic fever with renal syndrome in Eurasia and supposedly in Africa, and hantavirus cardio-pulmonary syndrome in the Americas. The relationship between the virus and its host species is a result of a several million year co-evolution. Although virus replication is most intense in the infected rodents' lungs, these animals do not develop disease, instead they carry and spread the pathogens throughout their lifetime by body fluids. In the majority of infections, the virus gets into the human body by vaporization of rodent body fluids or by direct contact. In Europe, Puumala (PUUV) and Dobrava-Belgrade (DOBV) hantaviruses are the most abundant hantaviral infectious agents. There are numerous studies described the presence of different genotipes of hantaviruses circulating in Hungary. Although the number of clinical and epidemiolgical studies are limited, the medical importance - especially in a high risk population - of these viruses are unqustionable. There are a variety of methods to identify hantaviral infections. Molecular biological methods (RT-PCR) - also enabling genotyping - and virus neutralization tests proved to be the most reliable tools. The latter technique requires virus culturing, which can only be carried out in high-containment laboratories.]

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Clinical Neuroscience

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

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]

Clinical Neuroscience

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.

Clinical Neuroscience

Autonomic nervous system may be affected after carpal tunnel syndrome surgery: A possible mechanism for persistence of symptoms after surgery

ONDER Burcu, KELES Yavuz Betul

After carpal tunnel surgery, some patients report complaints such as edema, pain, and numbness. Purpose – The aim of this study was to evaluate autonomic nervous system function in patients with a history of carpal tunnel surgery using sympathetic skin response (SSR). Thirty three patients (55 ±10 years old) with a history of unilateral operation for carpal tunnel syndrome were included in the study. The SSR test was performed for both hands. Both upper extremities median and ulnar nerve conduction results were recorded. A reduced amplitude (p=0.006) and delayed latency (p<0.0001) were detected in the SSR test on the operated side compared to contralateral side. There was no correlation between SSR and carpal tunnel syndrome severity. Although complex regional pain syndrome does not develop in patients after carpal tunnel surgery, some of the complaints may be caused by effects on the autonomic nervous system.

Clinical Neuroscience

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.