Lege Artis Medicinae

[Longissima via]

NAGY Zsuzsa

SEPTEMBER 20, 2002

Lege Artis Medicinae - 2002;12(09)

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Lege Artis Medicinae

[The effect of angiotensin receptor antagonists in diabetic nephropathy]

BÍBOK György

[Influencing the renin-angiotensin system through receptor blockade has become a new therapeutic approach toward the treatment of several morbidities, i.e. hypertension, cardiac failure and diabetic nephropathy. The current paper reviews the importance of diabetic nephropathy, the physiology of the renin-angiotensin system and specific effects of receptor blockade on different organs based on 3 new studies (published last year) using angiotensin-II receptor blockers. The paper gives a summary of the IRMA, IDNT and RENAAL studies, including their clinical and therapeutic significance in general practice as well as in specialized diabetes care. The new therapeutic approach (with an excellent safety profile, and infrequent side effects) could delay the progression or might even prevent the manifestation of diabetic nephropathy not only with lowering blood pressure but with its direct effects on target tissues as well. The angiotensin-II receptor blocking agents might be useful for the treatment of cardiac failure in hypertensive patients.]

Lege Artis Medicinae

[Drug treatment possibilities in chronic liver diseases]

HAGYMÁSI Krisztina, LENGYEL Gabriella, FEHÉR János

[Alcoholic and drug induced liver diseases, nonalcoholic steatohepatitis, hepatitis C and B chronic hepatitis, autoimmune diseases (primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis) and metabolic disorders (hemochromatosis, Wilson's disease) are the main chronic liver diseases. Authors summarize, based on the latest literature data, the medications of chronic liver diseases, emphasizing the treatment of the everyday practice. Natural and synthetic antioxidants are approved for the treatment of chronic alcoholic liver diseases besides abstinence, with diet of adequate quality and quantity. Nucleoside analogues (lamivudin) are recommended for the first-line therapy of the treatment of chronic hepatitis B. Interferon is presently considered the optimal treatment for only certain patients. Interferon and ribavirin combined therapy is well-established in the treatment of chronic hepatitis C. Ursodeoxycholic acid is the beneficial treatment option for primary biliary cirrhosis and primary sclerosing cholangitis. Prednisolon and azathioprine constitute the basic therapy of autoimmune hepatitis. Presumably, in the future, new strategies based on immunosuppressive combinations will play a crucial role. The chelating deferoxamine has less important part in the treatment of hemochromatosis. D-penicillamine still plays principle role in the medication of Wilson's disease.]

Lege Artis Medicinae

[Reference price system as a potential method for pharmaceutical cost containment]

KALÓ Zoltán, VINCZE Zoltán, LOVAS Kornélia, BODROGI József

[Reference pricing is one of the potential cost containment methods for pharmaceuticals. Authors describe its main types and the international examples of reference pricing together with technical details of its introduction. Consequences of the system are grouped into 5 categories: pharmaceutical expenditure, other health care expenditure, medical implications, consequences on patients and their health status, and political effects. They propose that reference pricing should be introduced only gradually based upon recommendations by multiprofessional teams. The system should be evidence based which includes clinical effectiveness, safety, compliance and cost-effectiveness. ”Real” active substance based reference pricing is justifiable for broad ranges of pharmaceuticals. General introduction of therapeutic reference pricing in Hungary, however, may result in serious negative consequences.]

Lege Artis Medicinae

[QT dispersion - the surface ECG marker of arrhythmic risk]

KUN Csaba, CZURIGA István, LŐRINCZ István

[During the past decade numerous publications have reported the pathophysiological and clinical value of QT dispersion. Increased QT dispersion was observed to be associated with proarrhythmic drug effects, prediction of mortality in heart failure and risk assessment after acute myocardial infarction. Based on the results of the repolarization process research and other significant clinical studies, the meaning and the usefulness of QT dispersion seems to be challenged. The original concept of portraying QT dispersion as a direct measure of regional heterogeneity of myocardial refractoriness is seriously flawed. At the same time, disproving this concept is not a good reason for stating that QT dispersion does not exist. The measurement of QT dispersion seems to be an approximate expression of repolarization abnormalities and should not be taken as a gold standard for a noninvasive estimate of repolarization abnormalities. However, we presently have no decent and widely available alternative to address repolarization abnormalities in standard 12-lead ECG. The authors present the pathophysiological meaning of QT dispersion, the controversies of automatic and manual methodology and the possible clinical relevances based on the most recent studies.]

Lege Artis Medicinae

[Cytological and genetic background of senescence]

LÁSZLÓ Valéria, FALUS ANDRÁS

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Clinical Neuroscience

The effects of 30 Hz, 50 Hz AND 100 Hz continuous theta burst stimulation via transcranial magnetic stimulation on the electrophysiological parameters in healthy individuals

OZDEMIR Zeynep, ACAR Erkan, SOYSAL Aysun

Transcranial magnetic stimulation is a non-invasive procedure that uses robust magnetic fields to create an electrical current in the cerebral cortex. Dual stimulation consists of administering subthre­shold conditioning stimulation (CS), then suprathreshold test stimulation (TS). When the interstimulus interval (ISI) is 1-6 msec, the motor evoked potential (MEP) decreases in amplitude; this decrease is termed “short interval intracortical inhibition” (SICI); when the ISI is 7-30 msec, an increase in MEP amplitude occurs, termed “short interval intracortical facilitation” (SICF). Continuous theta burst stimulation (cTBS), often applied at a frequency of 50 Hz, has been shown to decrease cortical excitability. The primary objective is to determine which duration of cTBS achieves better inhibition or excitation. The secondary objective is to compare 50 Hz cTBS to 30 Hz and 100 Hz cTBS. The resting motor threshold (rMT), MEP, SICI, and SICF were studied in 30 healthy volunteers. CS and TS were administered at 80%-120% and 70%-140% of rMT at 2 and 3-millisecond (msec) intervals for SICI, and 10- and 12-msec intervals for SICF. Ten individuals in each group received 30, 50, or 100 Hz, followed by administration of rMT, MT-MEP, SICI, SICF immediately and at 30 minutes. Greater inhibition was achieved with 3 msec than 2 msec in SICI, whereas better facilitation occurred at 12 msec than 10 msec in SICF. At 30 Hz, cTBS augmented inhibition and suppressed facilitation, while 50 Hz yielded less inhibition and greater inter-individual variability. At 100 Hz, cTBS provided slight facilitation in MEP amplitudes with less interindividual variability. SICI and SICF did not differ significantly between 50 Hz and 100 Hz cTBS. Our results suggest that performing SICI and SICF for 3 and 12 msec, respectively, and CS and TS at 80%-120% of rMT, demonstrate safer inhibition and facilitation. Recently, TBS has been used in the treatment of various neurological diseases, and we recommend preferentially 30 Hz over 50 Hz cTBS for better inhibition with greater safety and less inter-individual variability.

Clinical Neuroscience

Mid-term oral isotretinoin therapy causes a predominantly sensory demyelinating neuropathy

ALTUN Yasar, INAN Esra

Aim - The purpose of this prospective study was to investigate whether mid-term treatment with oral isotretinoin may impact peripheral nerve function. Methods - In this study, we included 28 patients with no apparent neurological or neurophysiological findings. The patients received treatment with oral isotretinoin for papulopustular or nodulocystic acne. The patients with normal findings in the first examination were given 1 mg/kg/day oral isotretinoin. Neurological examinations and electroneurographic studies were performed before and 6 months after the onset of isotretinoin treatment. Results - Clinical examinations and electroneurographic evaluations prior to treatment revealed no abnormalities in any of the patients. However, 20 patients (72%) displayed one or more abnormal values in the tested parameters after treatment. Although the mean amplitudes of compound muscle action potential of the ulnar and median nerves did not vary, significant decreases were observed in the mean sensory conduction velocities of median, ulnar, sural, medial plantar, medial dorsal cutaneous, and dorsal sural nerves 6 months after the onset of treatment. Conclusion - Systemic use of isotretinoin may cause electroneurographic changes. Probable electroneurographic alterations may be detected at a much earlier period via dorsal sural nerve tracing when electrophysiological methods used in routine clinical practice cannot detect these changes.

Clinical Neuroscience

Is isolated hand weakness associated with subtypes of stroke?

YILDIRIM Ahmet, GÜNGEN Dogan Belma

Background and aim - Isolated hand weakness is an uncommon condition in stroke patients. It is frequently confused with peripheral nerve system (PNS) pathologies; misdiagnosis may delay identification of the etiology and treatment of stroke. Herein, we aimed to underline the necessity of keeping the diagnosis of stroke in mind in case of patients with isolated hand weakness and to assess the etiology of stroke. Materials and methods - A total of eight patients (four females and four males), who are presented with isolated hand weakness and had acute cortical infarction documented via cranial MRI, were enrolled in the study. Demographic characteristics, physical and radiological findings of the patients, as well as the lateralization and etiology of infarction were evaluated. Results - The mean age of the patients was 61.8 ± 12 years. Isolated hand weakness was in the dominant hand in four patients. According to the etiology and clinical signs, the stroke was cardioembolic in three patients and they had predominant radial-side (thumb and index) finger weakness. Large vessel atherosclerosis was present in three patients; two patients with predominant ulnar-side (little and ring) finger weakness and one patient with uniform finger weakness; there were two patients with stroke of undetermined etiology and they had uniform finger weakness. Conclusion - Keeping stroke in mind together with PNS pathologies in case of isolated hand weakness is critical for early diagnosis and treatment of the patients. In addition, cardioembolic focus should be considered in case of predominant radial-side finger weakness, whereas particular attention should be paid to carotid artery diseases in case of predominant ulnar-side finger weakness.

Clinical Neuroscience

Functional neurotoxicity and tissue metal levels in rats exposed subacutely to titanium dioxide nanoparticles via the airways

HORVÁTH Tamara, VEZÉR Tünde, KOZMA Gábor, PAPP András

Introduction and aims - Nanoparticles of titanium dioxide are suspected neurotoxic agents and have numerous applications possibly resulting in human exposure by several ways including inhalation. In the present work, rats were exposed to spherical TiO2 nanoparticles of two different sizes by the intratracheal route. It was investigated how the neuro-functional alterations, detected by electrophysiological and behavioral methods, were related to the concentration of Ti in the tissue samples and what the influence of the size of the NPs was. Materials and methods - Rats (young adult Wistar males, 10/group) were exposed to TiO2 nanoparticles of ca. 10 and 100 nm diameter (suspension medium: neutral PBS with 1% hydroxyethyl cellulose) by intratracheal instillation in 5 and 18 mg/kg b.w. dose; 5 days per week for 6 weeks. Controls were instilled with saline, and vehicle controls, with the suspension medium. To see general toxicity, body weight was checked daily, and organ weights were measured at the end of experiment. Grip strength test, to assess motor function damage, was done before and after the 6-week treatment. Finally, the rats were anesthetized with urethane, spontaneous cortical activity and sensory evoked potentials were recorded, then the rats were dissected and tissue samples were taken for Ti level measurement. Results - Body weight gain indicated no general toxicity, and no significant change in the relative organ weights, except that of the lungs, was seen. However, change of time-to-fall in the grip strength test, and latency of cortical evoked po­tentials, were altered in the treated groups, indicating functional damage. Correlation of these alterations with the cortical Ti level was dissimilar for the two sizes of nanoparticles. Conclusion - The results provided further support to the functional neurotoxicity of TiO2 nanoparticles. The exact role of particle size, and the mechanisms involved, remain to be elucidated.

Lege Artis Medicinae

[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.]