Hypertension and nephrology

[Examination of nitrogen monoxide syntase in hypoxia induced conditions]

RUSAI Krisztina

OCTOBER 20, 2010

Hypertension and nephrology - 2010;14(05)

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Hypertension and nephrology

[The role of vitamin D receptor and the risk reducing effect of vitamin D receptor agonists in chronic kidney disease]

KISS István, KULCSÁR Imre, BARABÁS Noémi, KERKOVITS Lóránt

[Vitamin D3 is produced in the skin and is modified in the liver and kidney to the active metabolite form, 1,25-dyhydroxyvitamin D3 (calcitriol). Calcitriol binds to a nuclear receptor, the vitamin D receptor (VDR), and activates processes that bind to vitamin D. The classical effects of vitamin D receptor activator or agonist (VDRA) therapy for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease primarily involves suppressive effects on the parathyroid gland, and regulation of calcium and phosphorus absorption in the intestine an mobilization in bone. Several VDR agonists have been developed for the treatment of osteoporosis, hyperparathyroidism secondary to chronic kidney disease (CKD), and psoriasis. Secondary hyperparathyroidism (SHPT) is a common and serious consequence of CKD. SHPT is a complex condition characterized by a decline in 1,25-dihidroxi vitamin D and consequent VDR activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drug used for treatment of SHPT (non-selective and selective VDR activators, and calcimimetics). Observational studies in hemodialysis patients report improved cardiovascular and allcause survival among those received VDRA therapy compared with those not on VDRA therapy. The survival benefits of selective VDRA paricalcitol appear to be linked to "non classical" action of VDRA, possibly through VDRA-mediated modulation of gene expression. VRDAs are reported to have beneficial effects such as anti-inflammatory and antithrombotic effects, inhibition of vascular calcification and stiffening, inhibition of vascular smooth muscle cell proliferation, and regression of left ventricular hypertrophy. VDRA are also reported to negatively regulate the renin-angiotensin system, which plays a key role in hypertension, myocardial infarction and stroke. Data from epidemiological, preclinical and clinical studies have shown that vitamin D and/or 25(OH) vitamin D deficiency is associated with increased risk for cardiovascular disease (CVD). The selective VDR agonists are associated direct protective effects on glomerular architecture and antiproteinuric effects in response to renal damage. Emerging evidence suggest that VDR plays important roles in modulating cardiovascular, immunological, metabolic and other function. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD.]

Hypertension and nephrology

[Recent developments in the diagnosis and therapy of haemolytic uremic syndrome. Part 1: Diagnosis and initial therapy]

PROHÁSZKA Zoltán, SZILÁGYI Ágnes, SZABÓ Melinda Zsuzsanna oh., RÉTI Marienn, REUSZ György

[In this summary an overview is offered on the recent developments of the investigation and the treatment of hemolytic uremic syndrome. Based on the recent developments in the understanding of the pathogenesis and on the novel diagnostics there is an increasing ability to identify the etiology of specific diagnostic sub-groups of the disease. This molecular etiology-based classification and sub-group diagnosis has substantial influence on the short-term and long-term management of the affected patients. The first part of our review focuses on the steps of first and second line diagnosis and the selection between available therapeutic options, and provides flow-charts for the daily work. The various aspects of the long-term management and disease monitoring in hemolytic uremic syndrome will be reviewed in a second article in the future.]

Hypertension and nephrology

[Biosimilar erythropoietins in nephrology - benedictio seu maledictio?]

KISS István

[Biological medicines of protein or polypeptide origin produced with biotechnology are far more complex in structure than the low molecular weight chemical ones. In conjunction with chemical drugs generic copies are completely the same, while in the field of biological medicines only similarity can be stated, as identical molecules cannot be produced. Spatial structure, isomers and side chains cause difference and for this reason these are called biosimilar drugs. Immunogenity of biosimilar drugs is very different and the risk of antibody production against them is diverse. Pure red cell aplasia, a rare side effect of erythropoietins is a life-threatening condition so every effort must be done for its prevention. Biosimilar drugs are not to be replaced with each other, and even the reference drugs should not be substituted in order to identify easily the side effects of each drug. Importantly financing should support these clinical principles namely a cheaper drug could be started as a new treatment but a former treatment should not be replaced because of cost sensitivity. It is important to provide the availability of the very expensive biologically active drugs to each patient but it is acceptable that the treatment should be as cost-effective as possible. Similarly to the generic copy program of chemical drugs biosimilar drugs are also important for the clinical practice, however their use needs appropriate regulation and farmacovigilance.]

Hypertension and nephrology

[Chronic kidney disease and atherosclerosis]

REIBER István

[Accelerated cardiovascular disease is a frequent complication of chronic kidney disease. Chronic kidney disease promotes hypertension and dyslipidaemia, which in turn can contribute to the progression of renal failure. Diabetic nephropathy is a leading cause of renal failure. Hypertension, dyslipidaemia and diabetes together are the major risk factors of the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease. Promoters of calcification are increased and inhibitors are reduced, which favors vascular calcification, an important cause of vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke and peripheral arterial disease.]

Hypertension and nephrology

[Kidney transplantation in Hungary, 2010]

LANGER Róbert, TORONYI Éva

[Hungarian kidney transplantation has been established with three milestone operations. In 1902 Emerich Ullmann showed the technical feasibility of renal transplantation on dogs, and later the living donor transplant of András Németh in 1962 and the program starting operation of Ferenc Perner in 1973 already meant the real possibility for Hungarian patients. More than 5000 kidney transplantations were done since, and the operations are now made at the four university medical schools centers. In 2009 248 renal transplantations were done in our country (Budapest: 148, Szeged: 51, Pécs: 39, Debrecen: 34), from which 24 were living donor and nine combined kidney-pancreas cases. Despite the worsening financing situation in the health care system the numbers of transplantations are stable within a 15 year period, but this means a marked decrease in international comparison. In our country, the ratio of living donation is low, there is no paired donation, incompatible transplantation, the problems of hypersensitive patients are unresolved, and there is no old-for-old program. The solution to all of these problems could be joining to Eurotransplant, which is the definite wish of the transplant society based on the positive Slovenian and Croatian examples.]

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Clinical Neuroscience

Cases of inborn errors of metabolism diagnosed in children with autism

CAKAR Emel Nafiye, YILMAZBAS Pınar

Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism. One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. The personal information, routine and specific metabolic tests of the patients were analyzed retrospectively. Out of the 3261 patients who presented to our outpatient clinic, 179 (5.48%) were diagnosed with autism spectrum disorder and were included in the study. As a result of specific metabolic examinations performed, 6 (3.3%) patients were diagnosed with inborn errors of metabolism. Two of our patients were diagnosed with classical phenylketonuria, two with classical homocystinuria, one with mucopolysaccharidosis type 3D (Sanfilippo syndrome) and one with 3-methylchrotonyl Co-A carboxylase deficiency. Inborn errors of metabolism may rarely present with autism spectrum disorder symptoms. Careful evaluation of the history, physical examination and additional findings in patients diagnosed with autism spectrum disorder will guide the clinician in the decision-making process and chose the appropriate specific metabolic investigation. An underlying inborn errors of metabolism may be a treatable cause of autism.

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.]

Lege Artis Medicinae

[Diagnosis and treatment of microvascular coronary heart disease. Specialities of conditions in Hungary]

SZAUDER Ipoly

[Invasive investigations show that in two-thirds of patients the myocardial ischaemia persists without obstructive coronary disease and any other heart conditions (INOCA). The underlying cause may be microvascular dysfunction (CMD) with consecutive microvascular coronary disease (MVD) and microvascular or epicardial vasospastic angina (MVA). The modern practice of clinical cardiology while using the developed non-invasive cardiac imaging permits exact measuring of the coronary flow with its characteristic indices. All of these improve the diagnosing of CMD-induced myocardial ischemia and provide opportunity to determine primary MVD cases. Since the recognition and treatment of MVD is significantly underrep­resented in the Hungarian medical care, the primary stable microvascular angina (MVA) is described in detail below with its modern invasive and non-invasive differential diagnosis and treatment, concerning especially its frequency provoked by high blood pressure and female coronary heart diseases. There are highlighted all recommended diagnostic procedures available under domestic conditions.]

Clinical Neuroscience

Atypical presentation of late-onset Sandhoff disease: a case report

SALAMON András , SZPISJAK László , ZÁDORI Dénes, LÉNÁRT István, MARÓTI Zoltán, KALMÁR Tibor , BRIERLEY M. H. Charlotte, DEEGAN B. Patrick , KLIVÉNYI Péter

Sandhoff disease is a rare type of hereditary (autosomal recessive) GM2-gangliosidosis, which is caused by mutation of the HEXB gene. Disruption of the β subunit of the hexosaminidase (Hex) enzyme affects the function of both the Hex-A and Hex-B isoforms. The severity and the age of onset of the disease (infantile or classic; juvenile; adult) depends on the residual activity of the enzyme. The late-onset form is characterized by diverse symptomatology, comprising motor neuron disease, ataxia, tremor, dystonia, psychiatric symptoms and neuropathy. A 36-year-old female patient has been presenting progressive, symmetrical lower limb weakness for 9 years. Detailed neurological examination revealed mild symmetrical weakness in the hip flexors without the involvement of other muscle groups. The patellar reflex was decreased on both sides. Laboratory tests showed no relevant alteration and routine electroencephalography and brain MRI were normal. Nerve conduction studies and electromyography revealed alterations corresponding to sensory neuropathy. Muscle biopsy demonstrated signs of mild neurogenic lesion. Her younger brother (32-year-old) was observed with similar symptoms. Detailed genetic study detected a known pathogenic missense mutation and a 15,088 base pair long known pathogenic deletion in the HEXB gene (NM_000521.4:c.1417G>A; NM_000521:c.-376-5836_669+1473del; double heterozygous state). Segregation analysis and hexosaminidase enzyme assay of the family further confirmed the diagnosis of late-onset Sandhoff disease. The purpose of this case report is to draw attention to the significance of late-onset Sandhoff disease amongst disorders presenting with proximal predominant symmetric lower limb muscle weakness in adulthood.