Lege Artis Medicinae



JULY 20, 2004

Lege Artis Medicinae - 2004;14(07)

[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.]



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[One of the forms of conservative treatment of incontinent patients is pharmacological therapy. The choice of medicine for the conservative treatment of an incontinent patient is based on the diagnosis formulated by applying the appropriate diagnostic procedures. As far as pharmacological treatment is concerned, it is for the treatment of incontinence caused by idiopathic and neurogenic involuntary detrusor contraction. There are medicines for everyday clinical practice, partly uroselective ones with mainly anticholinergic effects. In case of stress incontinence the reduction of the symptoms can be expected by using an agent that increases the tone of the closing muscle of the urethra. In overflow incontinence the aim of the pharmacological treatment is to reduce the overflow resistance.]

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[Athens: hopes and question marks]


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GYŐRFFY Zsuzsa, LŐRINCZ Jenő, ÁDÁM Szilvia, KOPP Mária

[INTRODUCTION - In Hungary the number of induced abortions is three times higher than in European Union countries. The exploration of the bio-psycho-social factors in the background of abortions may serve as an instrument to develop effective prevention. METHODS - The Hungarostudy 2002 national representative study included 12,634 interviewed subjects. The sample represents the Hungarian population above the age of 18, according to gender, age and geographical location. The aim of the health survey was to analyse the physical and psychological status of the Hungarian population as well as the psychosocial risk factors. The prevalence of abortion in the female sub-sample was 22%. We analysed the background factors of abortion with the help of a statistical analysis. RESULTS - The risk factors behind abortions can be grouped as: physical abuse on behalf of partners and/or parents, attachment disorder and early traumatisation, lack of social support, low financial status and inadequate social environment. These factors have all shown significant connection to abortions. Suicide attempts and suicidal thoughts, high Beck Depression (BDI) scores, smoking and alcohol consumption are also significant among those who had abortions. CONCLUSION - An important aim of the Hungarostudy 2002 survey and the follow-ups is to serve a more extensive and effective prevention by exploring the background factors of induced abortions.]

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[INTRODUCTION - In recent years a number of clinical trials have been proved that infliximab, a monoclonal chimeric antibody against tumour necrosis factor (one of the proinflammatory cytokines) is an effective induction and maintenance therapy in severe and fistulizing Crohn’s disease. The authors summarize the results of the first Hungarian, open, multicenter clinical trial with biological treatment of Crohn’s disease. PATIENTS AND METHODS - Overall 74 patients in 9 study-centers were enrolled and allocated into the following two groups: 29 patients (31%) with severe, active, therapy-resistent clinical picture of Crohn’s disease and 45 individuals (61%) showing fistulizing forms of the disease. Infliximab was administered iv. in a dose of 5 mg/kg body mass one single occasion in patients formed the first group and altogether three times in cases suffering of fistulizing form of the disease. RESULTS - In active Crohn cases infliximab exerted its beneficial effect within 4 weeks (58% of patients improved) which was most pronounced at week 8th (79% of the patients was in better condition). However, in cases of fistulizing form longer period is neccessary for developing the effect. In 76% of treated patients proved to be efficacious within 14 weeks but later on flare-ups were observed. Concomittantly administered immunsuppressive agents did not altered the beneficial effect of infliximab. CONCLUSIONS - The results are proving the benefit of infliximab induction therapy both in cases of severe, active or in fistulizing forms of the disease. The article reviews the indication of infliximab treatment and provides a „user’s guide” for practizing clinicians.]

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DURA Eszter

[Recent data suggest that the copper-containing semicarbazide-sensitive amine oxidase enzyme (SSAO) may play a role in vascular endothelial damage through conversion of certain endogenous monoamines, such as methylamine, into cytotoxic aldehydes, hydrogen peroxide and ammonia. SSAO is present in various human tissues and in the serum. Elevated SSAO activities have been reported in patients with both types of diabetes mellitus. We have demonstrated that the activity of serum SSAO is significantly higher in type 2 diabetic patients with high-risk proliferative diabetic retinopathy compared to those without retinopathy. Our clinical results support the hypothesis that elevated SSAO activity may be involved in the pathogenesis of microvascular diabetic late complications, such as retinopathy. The enzymatic conversion of the endogenous monoamines (e.g. methylamine, aminoacetone) into toxic aldehydes and hydrogenperoxide may be one of the possible mechanisms of the development of microangiopathy. Also, the vascular adhesion protein-1 (VAP-1) function of the molecule can cause leukostasis and leukocyte activation through increased leukocyte adhesion, resulting in worsening of the capillary circulation and hypoxia. Further prospective, larger studies are needed to elucidate the role of the possible association between serum SSAO activity and highrisk proliferative retinopathy in patients with type 2 diabetes. The pharmacological manipulation of SSAO activity might be an interesting new concept for prevention and treatment of diabetic retinopathy.]

Hypertension and nephrology

[Genetics of isolated steroid-resistant nephrotic syndrome - results of the two decades around the turn of the millennium]

TORY Kálmán, KERTI Andrea, REUSZ György

[Childhood steroid-resistant nephrotic syndrome (SRNS) is a devastating clinical condition which progresses to end-stage renal disease in 30-40% of the cases after a follow up of 10 years. Based on its etiology, two forms can be distinguished, an immune and a genetic form. During the last two decades, mutations of ten genes - encoding mainly podocyte proteins - were identified in the latter group. As the treatment in the immune and genetic forms are different, and only the identification of the causative mutation can reliably distinguish them, it is important to be familiarized with the genotype-phenotype correlations. The aim of the present review is to summarize our current knowledge on the phenotypes linked to the identified genes.]

Clinical Neuroscience

[Genetics and hemostasis in young stroke patients]


[Background and purpose - The classical risk factors did not explain all the possible ethiology of cerebral stroke. Genetic polymorphisms responsible for thrombophilia were implicated recently as risk factors of stroke. In this geneticoepidemiological study the author’s aim was to analyse the tendency of genetic polymorphisms to cluster in a cohort of young and elderly stroke patients and in healthy subjects in Hungary. Methods - 253 patients with stroke were compared with 173 healthy blood donors on the basis of genetic polymorphisms of platelet GP IIb/IIIa receptor (33 LeuPro), prothrombin gene G20210A, Factor V Leiden mutation, ACE I/D, methylenetetrahydrofolate reductase (MTHFR) and β fibrinogen gene G455A. These data were acquired using PCR. Questionnaires were used to investigate the family history and to determine the risk factor profile. The subtypes of stroke were analysed in a stroke cohort grouped according to different polymorphisms. Results - An increased frequency of GP IIIa heterozygousity was found as compared to a West-European stroke cohort (31% versus 19%). The prothrombin gene variant (2.9% European and 4.8% in Hungary) was also found to increase in frequency. In young stroke patients (age <50) compared with control subjects the odds ratios were higher: in prothrombin gene (OR: 4.9), in Leiden mutation (OR: 1.67), in fibrinogen gene (OR: 1.64) and in MTHFR(+/+) (OR: 1.58). Clustering of two polymorphisms could only be detected in young patients. These clustering polymorphisms were GP IIb/IIIa with prothrombin G20210A variant (OR: 6.74, 95% CI 1.1-18.2) and prothrombin gene variant with MTHFR (OR: 5.3, CI95 1.2-8.3). Conclusion - Selected and clustered genetic polymorphisms of haemostatic factors could be responsible for the high stroke morbidity in Central Europe. The presence and clustering tendency of these factors have been described in young stroke victims.]

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[A remarkably successful therapy with gliclazid treatment in type 2 diabetes mellitus]

KIS János Tibor

[INTRODUCTION - Sulfonylureas have become sidelined as second-line preparations as their use has been associated with an increased occurrence of weight gain and hypoglykaemia. In the case reported, however, therapeutic goals have been achieved with the use of gliclazid. CASE REPORT - A 45-year-old man with type 2 diabetes mellitus was using a metformin XR preparation. His HbA1c level was high and his main complaint was distention. His abdominal complaint was also obstructing his diet. Because of the high HbA1c level and overweight I initiated incretin-mimetic treatment. Due to the worsening of abdominal complaints I replaced the treatment with gliclazid, after thoroughly informing the patient. With gliclazid treatment the patient's abdominal complaints subdued, he was able to maintain his diet, lost 14 kg in three months and the parameters of his carbohydrate metabolism normalised. CONCLUSION - In case of abdominal complaints, a repeated anamnesis of the diet can reveal metformin intolerance. In such cases, the use of gliclazid can lead to therapeutic success with no gastrointestinal adverse effects.]

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[Interrelations between antidepressants and diabetes]

HARGITTAY Csenge, GONDA Xénia, MÁRKUS Bernadett, VÖRÖS Krisztián, TABÁK Gy. Ádám, KALABAY László, RIHMER Zoltán, TORZSA Péter

[Diabetes and depression are frequent comorbidities. They are a heavy burden by themselves, however, as comorbidities increase additionally the number of diabetes-related complications, morbidity, and mortality. In the background of interrelations, there are both well-known and hypothetical mechanisms. The aim of the present review is to outline these interrelations between antidepressants and diabetes and to discuss the effect of medications on carbohydrate metabolism respectively. Anti­depressant treatment on the one hand may improve mood, cognitive function and medication adherence leading to an improved glucose metabolism, on the other hand through their metabolic side effects, they may worsen carbohydrate metabolism. Concerning metabolic side effects, selec­tive serotonin reuptake inhibitors are the sa­fest, while tricyclic antidepressants and mo­noamine oxidase inhibitors should be administered under close monitoring. Se­rotonin and noradrenaline reuptake inhibitors may deteriorate gly­cae­mic control via increased noradre­nergic activation. Novel antidepressants, how­ever, have a neutral or positive impact on gly­caemic measures. Screening for and temporally adjusted treatment of depres­sion may decrease the risk of comorbidities ge­nerated complications. While caring for diabetic patients with depression, one should consider metabolic side effects of antidepressants and close monitoring of carbohydrate metabolism.]