Search results

LAM Extra for General Practicioners

JUNE 20, 2012

[THE DIABETIC FOOT SYNDROME: PATHOMECHANISM, CLINICAL PICTURE, CURRENT TREATMENT AND PREVENTION]

JERMENDY György

[Diabetic foot syndrome is a characteristic late complication of diabetes mellitus. It can develop in patients with type 1 as well as type 2 diabetes mellitus, especially in case of a long duration of diabetes and sustained poor metabolic state. Diabetic neuropathy plays a pivotal role in the pathomechanism, but vascular symptoms might also contribute to the complex clinical picture. For making the diagnosis, evaluation of complaints, performing physical examination and using simple tests for identifying both distal, somatosensory neuropathy and potential angiopathy are of great importance. Therapeutic approaches aim to achieve proper glycaemic control, as well as to ameliorate symptoms of neuropathy, improve peripheral blood supply by medicines, angioplasty or intervention radiological methods, fight against infections and off-load the foot. Surgical intervention might also be necessary, and in severe cases, amputation might be needed. The diabetic foot syndrome increases mortality risk in patients with diabetes. Complaints related to diabetic foot syndrome are often resistant to treatment and tend to recur. Thus, prevention with long-term, good metabolic control and protection of the foot are of particular importance.]

Lege Artis Medicinae

APRIL 20, 2012

[The diabetic foot syndrome: pathomechanism, clinical picture, current treatment and prevention]

JERMENDY György

[Diabetic foot syndrome is a characteristic late complication of diabetes mellitus. It can develop in patients with type 1 as well as type 2 diabetes mellitus, especially in case of a long duration of diabetes and sustained poor metabolic state. Diabetic neuropathy plays a pivotal role in the pathomechanism, but vascular symptoms might also contribute to the complex clinical picture. For making the diagnosis, evaluation of complaints, performing physical examination and using simple tests for identifying both distal, somatosensory neuropathy and potential angiopathy are of great importance. Therapeutic approaches aim to achieve proper glycaemic control, as well as to ameliorate symptoms of neuropathy, improve peripheral blood supply by medicines, angioplasty or intervention radiological methods, fight against infections and off-load the foot. Surgical intervention might also be necessary, and in severe cases, amputation might be needed. The diabetic foot syndrome increases mortality risk in patients with diabetes. Complaints related to diabetic foot syndrome are often resistant to treatment and tend to recur. Thus, prevention with long-term, good metabolic control and protection of the foot are of particular importance.]

Clinical Neuroscience

MARCH 30, 2012

[Botulinum neurotoxin-A therapy in migraine]

TAJTI János, SZOK Délia, TUKA Bernadett, CSÁTI Anett, KURIS Anikó, MAJLÁTH Zsófia, LUKÁCS Melinda, VÉCSEI László

[Although migraine is a common, paroxysmal, highly disabling disorder, the primary cause and the pathomechanism of migraine attacks are enigmatic. Experimental results suggest that activation of the trigeminovascular system is crucial in its pathogenesis. This activation leads to the release of vasoactive neuropeptides (calcitonin gene-related peptide - CGRP, and substance P - SP) and to neurogenic inflammation, and peripheral and central sensitisation are expressed. Botulinum neurotoxin-A (BoNT-A), a potent toxin produced by Clostridium botulinum, affects the nervous system through specific cleavage of the soluble NSF-attachment protein receptor complex (SNARE), like synaptosomal-associated protein of 25 kDa (SNAP-25). The result of this multistage process is blockade of the presynaptic release of pain neurotransmitters such as CGRP, SP and glutamate. A pooled analysis of the data from two programmes of Phase 3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT 1 and 2) with BoNT-A in chronic migraine demonstrated significant benefit of BoNT-A over placebo with regard to the numbers of headache days and migraine episodes. BoNT-A diminished the frequency of acute headache pain medication intake, and resulted in reductions in headache impact and improvements in scores on the Migraine-Specific Quality of Life Questionnaire. The treatments with BoNT-A proved safe and were well tolerated.]

Clinical Neuroscience

MARCH 30, 2012

[Fingolimod therapy in multiple sclerosis - the issue of the pathomechanism]

TAR Lilla, VÉCSEI László

[Multiple sclerosis is an autoimmune inflammatory disease of the central nervous system with neurodegenerative chararacteristics. The newly discovered per os administrable drug fingolimod (FTY720) has a different mechanism of action than the current disease-modifying therapies. In vivo the drug binds to four out of the five sphingosine-1-phosphate receptors after phosphorylation. Fingolimod-phosphate (FTY720-P) causes internalization and degradation of the sphingosine-1-phosphate receptors in the membrane of lymphocytes thus in contrast to sphingosine-1-phosphate it acts like a functional antagonist. In experimental autoimmune encephalomyelitis - an animal model of multiple sclerosis - fingolimod blocks the sphingosine-1-phosphate gradient controlled lymphocyte egress from the lymph nodes and therefore reduces the peripheral lymphocyte count especially the encephalitogenic Th17 subset is reduced. Modulation of the sinus lining and blood-brainbarrier constructing endothelial cells also contributes to the complex mechanism of action. Additionally due to its liphohilic nature fingolimod is able to penetrate the blood brain barrier thus, beside its peripheral effects the drug can probably modulate the cells of the central nervous system directly. Presumably it can reduce neurodegeneration caused by astrogliosis through modification of astrocyte and oligodendrocyte activity. The results of current clinical studies are holding out with bright prospective in the aspect of either the favourable effects or the well tolerated side effects.]

Lege Artis Medicinae

FEBRUARY 20, 2012

[The role of antilipidaemic therapy in chronic kidney disease]

CSÁSZÁR Albert

[In chronic kidney disease (CKD), the risk of cardiovascular mortality is remarkably high, which is partly due to lipid alterations. The results with statin treatment in cardiovascular prevention studies and in CKD, and their metaanalysis show that antilipidaemic therapy decreases overall and cardiovascular mortality in the predialysed state. On the basis of the new study SHARP, coadministration of simvastatin plus ezetimib also significantly reduces the number of atherosclerotic events in predialysed CKD (this was the first positive hard-endpoint result regarding the combination), thus it can be considered as an alternative. A large-scale metaanalysis of two earlier studies assessing the dialysed patients and patients of the SHARP study who received only dialysis indicated that antilipidaemic therapy was successful, as the number of nonfatal myocardial infarctions and coronary revascularisation interventions have been significantly reduced. These new results also show that in patients who need dialysis, the efficiency of statin or statin plus ezetimib therapy is decreased compared to predialysed state - owing to the partly different pathomechanism -, but this antilipidaemic therapy - especially in those with a high cardiovascular risk - can reduce the incidence of cardiovascular events.]

LAM KID

DECEMBER 23, 2011

[Osteonecrosis of the jaws: real and unreal scares]

VASZILKÓ Mihály

[Osteonecrosis caused by bisphosphonates has been known for a long time, but it is still not widely known. Some people overestimate the danger caused by this disease, whereas others underrate it. In this paper, we summerise data from the international literature and our experiences concerning 93 patients treated at our clinic. We discuss the already known details of the pathomechanism of this disease, its risk factors, the diagnostic methods, the specific stages of the disease and the treatment approaches. Considering the difficulties of treatment, we can't emphasise enough the importance of prevention, since the development of this complication can be minimised even in patients at risk with dental sanation before the bisphosphonate therapy and/or with further intervention performed with antibiotic preventive therapy. We must also point out the importance of early diagnosis and of directing these patients to the appropriate specialist units.]

Clinical Neuroscience

NOVEMBER 30, 2006

[THE MODULATORY EFFECT OF ESTROGEN ON THE CAUDAL TRIGEMINAL NUCLEUS OF THE RAT IN AN ANIMAL MODEL OF MIGRAINE]

VARGA Hedvig, PÁRDUTZ Árpád, TAJTI János, VÉCSEI László, JEAN Schoenen

[Migraine is one of the most common neurological disorder affecting up to 14% of the population. The disease shows sexual dimorphism, thus gonadal steroids may play an important role in its patophysiology. One model of migraine headache is the systemic administration of nitric oxide (NO) donor nitroglycerin (NTG), which triggers a delayed attack without aura in many migraine patients but not in healthy volunteers. NTG is also able to activate the neurons of the caudal trigeminal nucleus in the rat. In our review we summarise the effect of NTG on the expression of some molecules, in the superficial laminae of the spinal portion of trigeminal nucleus caudalis, which play an important role in the pathomechanism of headaches, and the modulatory effect of chronic estradiol treatment. Our data show that NTG was able to modify all the examined substances in the caudal trigeminal nucleus, while chronic estradiol treatment abolished this effect. These data may help to understand the mechanisms by which estrogens influence trigeminal nociception and how nitric oxide triggers migraine attacks.]

Lege Artis Medicinae

JANUARY 20, 2010

[The changing concept of the metabolic syndrome in the past two decades]

HALMOS Tamás, SUBA Ilona

[The introduction of the concept of the metabolic syndrome (MS) (1988) had a great significance from both a theoretical and a clinical point of view. The concept and the assesment of this syndrome has been widely criticized during the past two decades, however, many new components and even new diseases have been added to its defintion. These significant changes motivated us to complete and modify our previous review on this topic published in this journal more than ten years ago. In addition to the classical concept of MS, we discuss its various definitions, in which no consensus has been reached. Besides the two characteristic features, insulin resistance and hyperinsulinism, we discuss the etiological role of endothelial dysfunction, overactivity of the symphato-adrenal system, endocrine activity of the adipose tissue, and low-degree inflammation. We also discuss the roles of the Peroxisome- Proliferator Activated Receptor system and the ubiquitin proteasome system in certain metabolic and inflammatory processes. Recently, the causal unity of the syndrome has been questioned, which has generated an extended and still ongoing debate. For the clinicians, however, the most important fact is that individuals with the characteristic symptoms of the syndrome represent a significant number of the population and are at hight risk of severe cardiovascular conditions. Finally, we outline the newly discovered relationships of the syndrome with other diseases that have a great public health importance, such as cancers, Alzheimer disease, sleep apnoe, nonalcoholic fatty liver disease and chronic obstructive pulmonary disease. We also discuss the supposed common pathomechanisms of these conditions. These associations further increase the significance of MS in terms of both therapy and prevention.]

Lege Artis Medicinae

JULY 20, 2004

[THE GENETICS OF DIABETES MELLITUS]

KORÁNYI LÁSZLÓ, PÁNCZÉL Pál

[The number of diabetic patients will be doubled in the coming decades reaching 300 million for year 2025. The number of type 1 diabetics will also be increased but the majority of it will result from the increased number of type 2 diabetics. All types of diabetes are the consequence of a combination of genetic susceptibility and environmental factors, meaning that the prevention of diabetes epidemic cannot be done without the clarification of the genetic background. Significant progression has happened in the discovery of the genetic background of type 1 diabetes mellitus. It was helped by the etiologic classification of the disease: with the new classification the patient groups became more homogeneous. The HLA system is responsible for about 50-70% of the genetic risk while the effects of other genetic factors contribute 1-2% of the genetic susceptibility, respectively. Presently 25 gene regions are known as the different genetic factors of type 1 diabetes mellitus. Regarding the HLA system, the genes and pathomechanism causing the disease are not known. The classification of diabetes mellitus can be based on the HLA type while the predictability of type 1 diabetes mellitus is helped by the HLA type and the INS-VNTR. Much less is known about the genetic background of the polygenic type 2 diabetes mellitus. Its manifestation is now happening at younger age before. The best-fit genetic model consists of only a few genes with moderate effect superimposed on a polygenic background. Several „candidate” genes participating in the impaired insulin secretion and insulin action have already been investigated as the genes responsible for type 2 diabetes. These data showed the specificity in the population and most showed mild or modest association with the disease. Genomewide scans have resulted a number of significant diabetes susceptibility genes specific for a variety of populations, but these investigations have only resulted in the isolation of one gene (calpain 10) that is thought to contribute to type 2 diabetes. Most recent genomewide scans found loci on chromosome 20 in two different populations with significant segregation of type 2 diabetes. These loci are near to the region harboring the transcription factor hepatocyte nuclear factor genes. The transcription regulator HNF family is responsible for the regulation of the expression of several genes participating in the function of liver and pancreatic islet becoming a strong candidate for being a diabetes gene.]

Ca&Bone

JUNE 20, 2005

[Disturbance of bone development in experimental hepatic cirrhosis in growing rats]

FERENCZ VIKTÓRIA, HORVÁTH CSABA, FOLHOFFER Anikó, KÁRI Béla, GAÁL János, MÉSZÁROS SZILVIA, WOLF Zsuzsanna, MESTER Ádám, HEGEDÛS Dalma, HORVÁTH Andrea, SZALAY Ferenc

[INTRODUCTION -The pathomechanism of hepatic osteopathy is not fully understood.We investigated how bone parameters change in growing rats with experimentally induced fatty liver, liver cirrhosis and hepatocellular carcinoma. METHODS - Liver disease was induced by administration of CCl4 and phenobarbital (PB) following a single injection of diethylnitrosamine (DEN) in 55 Fischer 344 rats.Animals were sacrificed and their femur removed at week 8 or 16. Bone mineral content (BMC), femoral length, cortical index (ratio of cortical thickness and total diameter at the diaphysis) and ultimate bending load (Fmax) of femora were determined. Results of animals treated with DEN+PB+CCl4 (group DPC, n=21) were compared to untreated animals (n=14) and to a second control group treated only with DEN+PB (group DP, n=20). RESULTS - Fatty liver and cirrhosis developed in each animal in the DPC group (n=21) at week 8 and in a subgroup of these animals (n=11) hepatocellular carcinoma also appeared by week 16. No changes in bone parameters were observed in this group at week 8, but lower BMD, femoral length, cortical index and Fmax values were found at week 16 compared to the untreated controls or to the DP group (p<0.05 for both). In the DP group no fatty liver or cirrhosis was observed at any time. Femoral length and Fmax values were higher in the DP group at week 8 compared to the untreated controls (p<0.05 for both).At week 16, however, no difference could be detected. CONCLUSION - Experimentally induced liver cirrhosis and hepatocellular carcinoma are associated with growth inhibition and reduced bone mineral content, cortical index and mechanical resistance in growing rats.]