Focusing on the 5F-MDMB-PICA, 4F-MDMB-BICA synthetic cannabinoids and their primary metabolites in analytical and pharmacological aspects.

Nowadays, more and more new synthetic cannabinoids (SCs) appearing on the illicit market present challenges to analytical, forensic, and toxicology experts. For a better understanding of the physiological effect of SCs, the key issue is studying their metabolomic and psychoactive properties. In this study, our validated targeted reversed phase UHPLC-MS/MS method was used for determination of urinary concentration of 5F-MDMB-PICA, 4F-MDMB-BICA, and their primary metabolites. The liquid-liquid extraction procedure was applied for the enrichment of SCs. The pharmacological characterization of investigated SCs were studied by radioligand competition binding and ligand stimulated [35S]GTPγS binding assays. For 5F-MDMB-PICA and 4F-MDMB-BICA, the median urinary concentrations were 0.076 and 0.312 ng/mL. For primary metabolites, the concentration range was 0.029-881.02* ng/mL for 5F-MDMB-PICA-COOH, and 0.396-4579* ng/mL for 4F-MDMB-BICA-COOH. In the polydrug aspect, the 22 urine samples were verified to be abused with 6 illicit drugs. The affinity of the metabolites to CB1R significantly decreased compared to the parent ligands. In the GTPγS functional assay, both 5F-MDMB-PICA and 4F-MDMB-BICA were acting as full agonists, while the metabolites were found as weak inverse agonists. Additionally, the G-protein stimulatory effects of the full agonist 5F-MDMB-PICA and 4F-MDMB-BICA were reduced by metabolites. These results strongly indicate the dose-dependent CB1R-mediated weak inverse agonist effects of the two butanoic acid metabolites. The obtained high concentration of main urinary metabolites of 5F-MDMB-PICA and 4F-MDMB-BICA confirmed the relevance of their routine analysis in forensic and toxicological practices. Based on in vitro binding assays, the metabolites presumably might cause a lower psychoactive effect than parent compounds.

Copper Accumulation in the Lips of Brass Players: Case Report of a Rare Phenomenon.

Work-related exposures affecting oral health are important factors of morbidity and decreased quality of life, which may emerge from numerous physical, chemical, or mental occupational exposures. Copper (Cu) is an important trace element, however, it may also cause allergies, depose and accumulate in the body, leading to acute and chronic toxicity. In the present report, we describe a rare phenomenon found during the examination of two professional brass players, after incidentally noting an artefact during magnetic resonance imaging (MRI) scans, which were performed to monitor bone healing after bone augmentation procedures in an unrelated clinical study. During a detailed workup of patient characteristics, data on medical history, lifestyle, professional habits related to playing the instrument, and oral health status were collected. Overall, both patients presented with similar histories, and the differences from the context of this study were not relevant; however, both brass players were using an uncoated Cu mouthpiece for over 15 years. Based on the imaging findings (a shadow in the area of the lips on the MRI images) and the organoleptic evaluation of the lips and mucosa of the individuals (temporary faint green discoloration), it is most likely that the brass players were affected by oxidized Cu accumulation in the lip. In contrast to several professions, musicians are usually not required by law to attend obligatory occupational health check-ups, which may facilitate the occurrence of such exposures in musicians. Clinicians should be on the lookout for brass players involved in the profession for a long time, who may have used the mouthpieces for an extended period of time, in addition to musicians affected by Wilson's disease. In patients affected by this phenomenon, diagnostics of oral cancer and prosthodontic procedures may be cumbersome, due to the detrimental impact on the utility of MRI imaging from artefact-formation and scattering.

Drug consumption of suspected drug-influenced drivers in Hungary (2016-2018).

The hazard caused by driving under the influence of drugs (DUID) is determined by the time of consumption, dose and biological effects of a substance, as well as by synergistic drug interactions after multi-drug use. The aim of this work was to investigate the prevalence and pattern of psychoactive substance use of suspected DUID drivers and to present the advantages and disadvantages of the system currently used for determination of impairment in Hungary. Blood and urine samples, collected between 2016 and 2018, were taken from 2369 drivers with a positivity rate of 95% for at least one substance. Classical illicit drugs were detected in 76-87%, prescription medications in 9-15%, stimulant New Psychoactive Substances (sNPS) in 3-8%, and synthetic cannabinoids (SCs) in 20-22% of the positive samples. The most frequent substances according to substance groups were: classical illicit drugs: cannabis (n = 1240), amphetamine and methamphetamine (AM/MA) (n = 753), MDMA (n = 196), and cocaine (n = 180), medicines: alprazolam (n = 188) and clonazepam (n = 83), sNPS: N-ethyl-hexedrone (n = 115), SCs: 5 F-MDMB-PINACA (n = 267), AMB-FUBINACA (n = 92) and ADB-FUBINACA (n = 90). The median age of classical illicit drugs users was 29 years, prescription medicine users were 33 years old, sNPS users were 28 years, and SC users were 26 years old. Compared to the previous two years, we found pronounced changes in the ratio of sNPS (14% decrease) and SC users (10% increase), and in the pattern of NPS consumption. The ratio of multi-drug use varied between 38% and 50%. 69% of drivers tested positive were deemed impaired. Impairment was determined according to impairment limits (80-82%), multi-drug use (12-13%), and the result of medical investigation when a single active substance with no set impairment limit was detected in the blood (6-8%). The results of medical investigations may be uncertain due to the long time delay between arrest and clinical examination and to the structure of medical investigations created for determination of alcoholic impairment. In conclusion, a revision of the current medical investigation protocol is warranted to standardize clinical symptom scores that better correlate with driving impairment.

Gift and informal payment to Hungarian nurses after the regulation changes in 2021. / A magyar egészségügyi szakdolgozóknak adott ajándék és "hálapénz" a 2021. évi jogi fordulat után.

Összefoglaló. Bevezetés: A magyar egészségügyi szakdolgozók hálapénzes szokásairól 2020-ban végzett kutatást követoen 2021-ben, a megváltozott jogszabályi környezetben is végeztünk felmérést, hogy kimutassuk az egészségügyi szakdolgozók jogköveto, etikus és empatikus hozzáállását. Célituzés: A 2021. május-júliusban végzett kérdoíves felmérés alapján kimutatni az ajándékozás módjait, összegét és egyéb szokásait az egészségügyi szakdolgozók körében, különös tekintettel arra, hogy ez a juttatás és elfogadás korrupciós buncselekménynek minosül. Módszer: 2021. május-júliusban 246 egészségügyi szakdolgozó kérdoíves felmérése történt meg a Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központjában a készpénzadás és ajándékozás formáinak és körülményeinek, valamint összegének megismerése érdekében. Az eredményeket elsosorban leíró statisztikai formában elemeztük, különös tekintettel a mutéti, a belgyógyászati és a gyermekgyógyászati szakterületek között mutatkozó különbségekre. Mindezt összevetettük a 2020-ban készült felmérésünk eredményeivel. Eredmények: A mutéti területen a visszautasított paraszolvencia átlagosan 13 250 Ft (cca. 38 euró) volt, amely magasabb összeg, mint a 2020-ban mért, akkor még legálisan elfogadott hálapénz. Hasonlóképpen jóval nagyobb összegeket utasítottak vissza a belgyógyászati és a gyermekgyógyászati területen muködo egészségügyi szakdolgozók 2021-ben, a megváltozott jogi szabályozás mellett, mint amennyit 2020-ban még törvényesen elfogadtak: belgyógyászati területen 13 467 Ft-ot (cca. 38 eurót), míg gyermekgyógyászati területen 13 286 Ft-ot (cca. 38 eurót) utasítottak vissza. Az ajándéktárgy átadása a kérdoívek adatai szerint 2021-re ritkábbá vált, mint a korábbi jogszabályi környezetben mért adatok szerint volt. Következtetés: Az egészségügyi szakdolgozók körében a készpénz visszautasítása és jobbára a kisebb értéku ajándéktárgyaknak a kezelést követo elfogadása jellemzo a 2021-tol megváltozott magyarországi jogszabályi környezetben. Orv Hetil. 2022; 163(9): 362-372. INTRODUCTION: After our research in 2020 on informal payments to nurses, we made a research in 2021, in a new legal environment, in order to demonstrate nurses' legal, ethical and empathetic behaviour. OBJECTIVE: We intended to highlight the manners, sums and other circumstances of gift given to nurses, based on a survey conducted in May-July 2021, with a special regard to the fact that informal payment now constitutes a crime of corruption. METHOD: In May-July 2021, we questioned 246 nurses in the Albert Szent-Györgyi Health Center of the University of Szeged, Hungary, in order to highlight the forms, circumstances, and sums of informal payments and gift giving. We analyzed the results by means of descriptive statistical methods, with special regard to the differences among surgical, internal medical and pediatric fields. We compared our results to those found in 2020. RESULTS: In surgical field, the average refused informal payment amounted to 13 250 forints (cc. 38 euros), which is higher than the sum measured in 2020. In internal medical care, 13 467 forints (cc. 38 euros), while in pediatric field, 13 286 forints (cc. 38 euros) were refused, which is also higher than in 2020. Gift giving in 2021 is rarer than before 2021. CONCLUSION: In the new legal environment in effect from 2021 in Hungary, the nurses tend to refuse informal payments and rather accept small gifts after treatment. Orv Hetil. 2022; 163(9): 362-372.

Clinical symptoms and blood concentration of new psychoactive substances (NPS) in intoxicated and hospitalized patients in the Budapest region of Hungary (2018-19).

BACKGROUND: New Psychoactive Substances (NPS) impose a new challenge on the legal and health care system, yet, there is little information available about how new substances spread based on hospitalization of intoxicated patients. The aims of this study were: (i) to investigate the frequency of NPS among suspected drug intoxicated patients, (ii) to study the connection between blood concentration and clinical symptoms, (iii) to determine their half-life with a time-series blood sampling protocol. METHODS: During the observation period, 116 suspected drug intoxicated patients were sampled. The samples were analyzed for alcohol, 20 classical illicit and licit drugs, and for 78 NPS. Clinical symptoms were registered on-site (by the Emergency Medical Services) and (also) at hospital admittance. RESULTS: NPS were detected in 51 patients of which cathinones were found in 4, the synthetic cannabinoids (SCs) 5 F-MDMB-PINACA and 5 F-MDMB-PICA in 23-23, and CUMYL-CH-MEGACLONE in 2 cases. Poison severity scores (PSS) showed mild to moderate intoxications overall. Connection between blood concentration and severity of clinical symptoms were inconclusive. The calculated half-life of 5 F-MDMB-PINACA and 5 F-MDMB-PICA was 2.50 and 2.68 h, respectively. CONCLUSION: The ratio of SCs among the selected intoxicated patients was higher than expected from seizure data which could be the consequence of targeted patient selection. The clinical symptoms and the severity of intoxication cannot be characterized simply by NPS blood levels. The short half-life of SCs can explain the relatively rapid consolidation of intoxication symptoms.HighlightsIn the Budapest region, the majority of hospitalized NPS intoxications was caused by the synthetic cannabinoids 5F-MDMB-PINACA and 5F-MDMB-PICA in 2018-19.No correlation between blood concentration and symptoms severity could be established.The clinical symptoms of synthetic cannabinoid users improved quickly and no ICU treatment was necessary.The half-life of 5F-MDMB-PINACA and 5F-MDMB-PICA was proved to be 2.50 hours and 2.68 hours, respectively.

The customs of acceptance of informal payments among Hungarian nurses / A hálapénzzel kapcsolatos szokások a magyar egészségügyi szakdolgozók körében.

Összefoglaló. Bevezetés: Magyarországon 2021. január 1-jétol a hálapénz minden formájának adása és elfogadása buncselekmény, kivéve a legföljebb a minimálbér 5%-át (8370 forintot) eléro ajándékot. Míg a tilalmat az orvosok esetében jelentos béremelés kompenzálja, addig a szakdolgozók korábban is kevéssé vizsgált hálapénzjuttatásának helyzetére és megváltozására vonatkozóan alig vannak adatok. Célkituzés: A szakdolgozói hálapénz 2020 végi kiinduló helyzetének feltárása és az új jogszabályi eloírások becsülheto hatásainak vizsgálata a szakdolgozók által nyújtott információ alapján. Módszer: 2020 oszén 167 egészségügyi szakdolgozó kérdoíves felmérése történt meg a Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központjában a hálapénzadás motivációinak, formáinak és körülményeinek, valamint összegének megismerése érdekében. Az eredményeket elsosorban leíró statisztikai formában elemeztük, különös tekintettel a mutéti, a belgyógyászati és a gyermekgyógyászati szakterületek között mutatkozó különbségekre; és összevetettük az új törvény hatására várható változásokkal. Eredmények: A 167 válaszadóból 93-an mutéti/operatív területen, 54-en belgyógyászati jellegu területen, 18-an pedig a gyermek/ifjúsági ellátásban dolgoznak. Mindegyik szakterületen megjelent a hála mellett a korrupciós célú juttatás, de ezzel és a hálapénzjelenséggel legkevésbé a gyermekgyógyászati terület volt érintett. A nagyobb értéku ajándék ritka, de a kisebb értéku rendszeresen alkalmazott juttatás. Egy hét benntartózkodás esetén a válaszadók átlagosan 10 851 forintot (36 USD) kaptak hálapénzként, míg egy-egy alkalommal 5326 forintot (18 USD). Az összegek - hasonlóan az orvosi hálapénzhez - jelentos eltérést mutattak az egyes területek között, a mutéti szakmákban pedig meghaladták az új törvényi korlátot. A magánellátásban kapott hálapénz kisebb arányú, a munkahelyen kívül átadott juttatás pedig kifejezetten ritka. Következtetés: A korrupciós célú hálapénz az egészségügyi szakdolgozói szférában ugyan jelen van, de nem jellemzo. A szakdolgozóknak juttatott hálapénz büntetojogi szankcionálását nem kompenzálja az orvosokéhoz hasonló béremelés. A pénzbeli juttatás ajándéktárgy formájában történo juttatása minden területen jelent veszteséget, a mutéti területen az értékben kifejezett veszteség is jelentosebb lehet. A büntetoeljárási fenyegetettség nem elegendo a magyarországi hálapénzrendszer megszüntetéséhez, további társadalompolitikai intézkedések szükségesek az egészségügyi dolgozók és a betegek attitudjének megváltoztatásához. Orv Hetil. 2021; 162(41): 1658-1668. INTRODUCTION: In Hungary, since January 1st, 2021, the giving and acceptance of all forms of informal payments constitute a crime, except for gifts of a value of no more than 5% of the minimal monthly salary. While in the case of physicians, a pay rise compensates the loss of revenue, we hardly have data on the nurses' attitude in relation to the acceptance of informal payments. OBJECTIVE: We intend to uncover the situation of informal payments at the end of 2020 and to examine the effects of the new legal regulation, based on information from nurses. METHOD: In the fall of 2020, we questioned 167 nurses in the Albert Szent-Györgyi Health Center of the University of Szeged, Hungary, in order to highlight the motivations, forms, circumstances, and sums of informal payments. We analyzed the results by means of descriptive statistical methods, with special regard to the differences among surgical, internal medical and pediatric fields. We analyzed the results with a view to the new legal regulations. RESULTS: Out of 167 respondents, 93 work in operative field, 54 in internal medical care, and 18 in pediatric care. Besides gratitude, corruption appeared in all the three fields, however, pediatric care was the least touched by corruption. Gifts of a higher value are rare, however, small gifts are common. The respondents received 10 851 HUF (i.e., 36 USD) as informal payment from in-patients after one week, while, occasionally, 5326 HUF (i.e., 18 USD). The sums - similarly to informal payments to physicians - vary from field to field in healthcare. In the surgical field, the sums surpassed the new legal limit. Informal payments are given in private healthcare more rarely than in public healthcare. Informal payments given outside the workplace hardly ever occur. CONCLUSION: The informal payment with the goal of corruption is present in the sphere of nurses, however, it is not typical. The criminal sanctioning of informal payments to nurses is not compensated by a pay rise similar to that of physicians. The fact that informal payments are substituted by gifts results in loss of revenue in all fields of healthcare, however, this loss is the most salient in the surgical field. The criminal sanctioning is not sufficient to eliminate informal payments in Hungary; further socio-political measures are to be taken with the goal to change the attitude of healthcare workers and patients. Orv Hetil. 2021; 162(41): 1658-1668.

Analytical Methodologies for the Characterization and Analysis of the Parent Compound and Phase I Metabolites of 4F-MDMB-BICA in Human Microsome, Urine, and Blood Samples.

4F-MDMB-BICA is one of the most dangerous new illicit synthetic cannabinoids (SCs) in 2020. Consumption of 4F-MDMB-BICA has been associated with a number of death cases and related serious adverse health effects in Hungary. Therefore, the use of reliable analytical methods to confirm the intake of 4F-MDMB-BICA is an important issue in forensic practice. Besides the detection of the parent compounds of SCs, the screening of their metabolites provides a reliable confirmation of their consumption, in particular, when the parent compound is under the limit of detection. To the best of our knowledge, this is the first report describing the identification of metabolites of 4F-MDMD-BICA after treatment with pooled human liver microsome (pHLM), and in human urine and blood samples using the combination of data obtained by comprehensive UHPLC-HRMS and semi-targeted UHPLC-HRMS/MS methods. Finally, our routine UHPLC-MS/MS method for screening urine and blood SCs was improved by adding the parent compound and selected main biomarkers of 4F-MDMD-BICA. From the pHLM assay of 4F-MDMD-BICA, 30 phase I metabolites were characterized and structural information thus obtained provided the basis of further identification of in vivo urine and blood metabolites. Overall, 20 urinary and 13 blood in vivo metabolites of 4F-MDMD-BICA have been identified by the investigation of five authentic urine and two blood samples. The ester hydrolysis metabolite was selected as a reliable primary biomarker in urine and blood. As secondary targets, urinary mono-hydroxylation metabolite and ester hydrolysis + dehydrogenation metabolite in blood were recommended due to their abundance and selectivity. Overall, the main phase I metabolites of 4F-MDMD-BICA were successfully characterized, and our routine analytical method with related sample preparation procedure provided a reliable analytical tool for screening both 4F-MDMD-BICA and its selected metabolites in urine and blood samples.

Fatal intoxication of a regular drug user following N-ethyl-hexedrone and ADB-FUBINACA consumption.

In Hungary, N-ethyl-hexedrone (NEH) was the most frequently seized stimulant designer drug in 2017, while among synthetic cannabinoids ADB-FUBINACA and AB-FUBINACA were the most popular. Symptoms of intoxication by these substances are well known but less is known about the pathology of overdose-related death. NEH-induced fatal intoxication has not been described in the literature and knowledge surrounding the particular circumstances of death could be useful better public education of risk and more adequate treatment of overdose patients. In this report, we characterize the case of a 23-year-old male regular drug user who died a few hours after NEH and ADB-FUBINACA consumption. His medical history showed arrhythmia in childhood, and some seizures. Autopsy found he had a BMI of 42.9, a hypertrophic and dilated heart, severe atherosclerosis of the valves, coronaries and the arteries, and edema of the internal organs. Histology confirmed those findings. Postmortem blood levels of NEH were 285 ng/ml, along with 0.08 ng/ml ADB-FUBINACA and five ADB-FUBINACA metabolites. Based on the blood concentrations measured in suspected drug users (≤83.9 ng/ml) we hypothesize that NEH intoxication was the cause of death in this case, with heart disease being a co-factor and that the synthetic cannabinoid effect might have been accompaniment. This case also offered the opportunity to identify the metabolites of ADB-FUBINACA in the blood. We identified metabolites in the post-mortem blood by comparing them to human liver microsomal enzyme metabolites in vitro. Three major and two minor metabolites were found in the blood, of which two could only be derived from ADB-FUBINACA, as opposed to other cannabinoids. The case highlights the importance of the complex analysis of drug related deaths by medico-legal autopsy, histopathology and toxicology.

Changes in illicit, licit and stimulant designer drug use patterns in South-East Hungary between 2008 and 2015.

The aim of this work is to present the changes in classical illicit and licit drug, as well as stimulant designer drug (SDD) consumption of suspected drug users in South-East Hungary between 2008 and 2015. Urine and/or blood samples of 2976 subjects were analyzed for these groups of substances of which 1777 (59.7%) were tested positive. THC was the most frequent (32.2%) substance, followed by classical stimulants (amphetamine, metamphetamine, MDMA, cocain) (21.4%), SDDs (17.0%), benzodiazepines (15.5%), medical opiates (codeine without morphine, methadone, tramadol) (4.03%), and morphine with or without 6-acethyl-morphine (1.98%). The annual rate of cannabis consumption continuously decreased after 2010. The use of classical stimulants was constant, except for a significant increase in 2015. Benzodiazepine incidence increased and remained steady after 2011. Medical opiate and morphine frequency was variable. SDDs were found in the highest number in 2012-13, exceeding the frequency of classical stimulants. The most prevalent SDDs were as follows: 2010 - mephedrone, 2011 - 4-MEC, methylone, MDPV, 4-FMC, and 4-FA, and 2012-2015 - pentedrone. Beside pentedrone, 3-MMC, αPVP, αPHP, and 4-CMC were detected with a notable number in this period. Multi-drug use was found in 30-43% of suspects tested positive between 2008 and 2014, which elevated to 52% in 2015. The frequency of substances in the biological samples corresponded to their seizure rate. When SDDs were included on the NPS list, their frequency in biological samples and in seized materials slightly decreased or did not change. However, a marked decrease was observed following classification as illicit drugs.

[Forensic aspects of sexul assault].

No abstcarct available.

The role of illicit, licit, and designer drugs in the traffic in Hungary.

The aim of this study was to investigate the prevalence and pattern of psychoactive substances among suspected DUID (Driving Under the Influence of Drugs) drivers in Hungary in 2014 and 2015. Blood and/or urine samples of 1252 suspected drivers (600 in 2014 and 652 in 2015) were analyzed for classical illicit and licit drugs, stimulant designer drugs (SDDs), and for synthetic cannabinoids, with 78.3% and 79.6% positive cases for at least one substance in 2014, and 2015, respectively. Impairment was proven in 39.2% (2014) and 35.7% (2015) of all drivers tested, based on the legal criteria of Hungary. Classical illicit drugs were found to be present in blood or urine of 89-61%, drivers tested. Drivers also tested positive for legal medications in 20-22%, SDDs in 21-28%, and synthetic cannabinoids in 15-19% of all cases. This indicates a drop in prevalence for classical illicit drugs and a slight but statistically non-significant increase for the other three substance groups. The distribution of drug types in each category were: [1] classical illicit drugs: cannabis (432), amphetamine (321), and cocaine (79); [2] medicines: alprazolam (94) and clonazepam (36); [3] SDDs: pentedrone (137) and α-PVP (33); [4] synthetic cannabinoids: AB-CHMINACA (46) and MDMB-CHMICA (30). The average age of illicit drug and SDD users was 30 years, while legal medications users were 36 years old on average, and the mean age of synthetic cannabinoid users was 26.5 years. The presence of both alcohol and at least one drug in samples was found in about 10% of the cases, both years. The ratio of multi-drug use was 33.0% in 2014 and 41.3% in 2015. Compared to former years the number of drivers who tested positive for drugs doubled in Hungary, but it is still low compared to alcohol positive cases. The relatively low detected rate of DUID can be explained by (1) combined alcohol consumption masking drug symptoms, (2) the absence of road-side tests for illicit and designer drugs and, (3) police officers not adequately trained to recognize milder symptoms of impairment. Targeted education of police officers, prompt medical examination and the use of a symptom-focused on-site survey, could improve the efficacy of DUID investigations. Our findings are not comparable with drug consumption habits of the general driving population. The last roadside survey (DRUID EU-6 Project) was performed in Hungary in 2008-2009, prior to the mass spreading of designer drugs. As their appearance has drastically changed the pattern of drug consumption of the population, a new roadside survey, targeting general drivers, would be necessary.

Genetic analysis of the SOD1 and C9ORF72 genes in Hungarian patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons. To date, more than 20 genes have been implicated in ALS, and of these, the 2 most frequently mutated are the superoxide dismutase 1 (SOD1) gene and the chromosome 9 open reading frame 72 (C9ORF72) gene. In this study, we aimed to investigate the contribution of these 2 Mendelian genes to the development of the disease in Hungarian ALS patients (n = 66). Direct sequencing of the SOD1 gene revealed a novel (p.Lys91ArgfsTer8) and 3 recurrent heterozygous mutations (p.Val14Met, p.Asp90Ala, and p.Leu144Phe) in 5 patients. The novel p.Lys91ArgfsTer8 mutation led to a frameshift causing the addition of 8 new amino acids, including a premature stop codon at position 99. The GGGGCC hexanucleotide repeat expansion of the C9ORF72 gene was present in 1 ALS patient. This study represents the first genetic analysis of 2 major ALS causative genes in a cohort of Hungarian ALS patients and contributes to the further understanding of the genetic and phenotypic diversity of ALS.

Different phenotypes in identical twins with cerebrotendinous xanthomatosis: case series.

Cerebrotendinous xanthomatosis (CTX) is a rare, genetically determined error of metabolism. The characteristic clinical symptoms are diarrhea, juvenile cataracts, tendon xanthomas and neuropsychiatric alterations. The aim of this study is to present a pair of identical adult twins with considerable differences in the severity of phenotype. With regards to neuropsychiatric symptoms, the predominant features were severe Parkinsonism and moderate cognitive dysfunctions in the more-affected individual, whereas these alterations in the less-affected patient were only very mild and mild, respectively. The characteristic increase in the concentrations of serum cholestanol and the lesion volumes in dentate nuclei in the brain assessed with magnetic resonance imaging were quite similar in both cases. The lifestyle conditions, including eating habits of the twin pair, were quite similar as well; therefore, currently unknown genetic modifiers or certain epigenetic factors may be responsible for the differences in severity of phenotype. This case series serves as the first description of an identical twin pair with CTX presenting heterogeneous clinical features.

[Forensic analysis of injuries in dentistry]. / Fogászati jellegu sérülések törvényszéki vizsgálata.

INTRODUCTION: Documentation and evaluation of dental injuries in forensic medicine are rather problematic. It needs a professional work up why dental injuries are out of focus, and how the diagnosis, pattern and treatment are influenced by novel approaches of dentistry. AIM: The aims of the authors were to characterize dental injuries, to compare their own findings to literature data concerning the type and characteristics of injuries, and propose a diagnostic workflow. METHOD: Expert's reports between 2009 and 2013 at the Department of Forensic Medicine, University of Szeged were reviewed. RESULTS: Review of about 7000 reports revealed only 20 cases with dental injury, which is in contrast with literature data indicating a significantly higher frequency of dental injuries. CONCLUSIONS: Although the number of "dental cases" was low, there were several additional cases where the trauma probably affected the teeth but the injury was not documented. In future more attention is needed in forensic evaluation of the mechanism, therapeutic strategy and prognosis of dental injuries.

Frequency and structure of stimulant designer drug consumption among suspected drug users in Budapest and South-East Hungary in 2012-2013.

Identification of abuse and frequency patterns of stimulant designer drugs (SDDs) provides important information for their risk assessment and legislative control. In the present study urine and/or blood samples of suspected drug users in criminal cases were analysed by GC-MS for 38 SDDs, and for the most frequent illicit and psychoactive licit drugs in Hungary. Between July 2012 and June 2013, 2744 suspected drug users were sampled in Budapest and during 2012 and 2013, 774 persons were sampled in South-East Hungary (Csongrád County - neighbour the Romanian and Serbian borders). In Budapest 71.4% of cases, and in South-East Hungary 61% of cases were positive for at least one substance. Pentedrone was the most frequent SDD in both regions; however, the frequency distribution of the remaining drugs was highly diverse. SDDs were frequently present in combination with other drugs - generally with amphetamine or other stimulants, cannabis and/or benzodiazepines. The quarterly distribution of positive samples indicated remarkable seasonal changes in the frequency and pattern of consumption. Substances placed on the list of illicit drugs (mephedrone, 4-fluoro-amphetamine, MDPV, methylone, 4-MEC) showed a subsequent drop in frequency and were replaced by other SDDs (pentedrone, 3-MMC, methiopropamine, etc.). Newly identified compounds from seized materials were added to the list of new psychoactive substances ("Schedule C"). While the risk assessment of substances listed in Schedule C has to be performed within 2 years after scheduling, continuous monitoring of their presence and frequency among drug users is essential. In summary, our results suggest which substances should be dropped from the list of SDDs measured in biological samples; while the appearance of new substances from seized materials indicate the need for developing adequate standard analytical methods.

Sudden cardiac death from parvovirus B19 myocarditis in a young man with Brugada syndrome.

Cardiovascular diseases are the leading cause of sudden death all over the world. The aetiology of sudden cardiac death among young adults includes Brugada syndrome and myocarditis. Brugada syndrome is a genetic abnormality of sodium channels in the myocardium with a characteristic electrocardiographic pattern. Myocarditis has several aetiologies including infections. One of the most common cardiotropic viruses is parvovirus B19. This infection presents as a febrile illness in childhood and may result in fatal outcome, more frequently in adults. In this report we present a case of a young man who suffered from a mild upper respiratory tract infection. After recovery he had an episode of syncope and was diagnosed with Brugada syndrome. Some weeks later he died suddenly at home while sleeping. The detailed forensic pathological, histological and microbiological investigation revealed a parvovirus B19-associated myocarditis. Synergic effect of structural and functional abnormalities of the myocardium may lead to death. The cause and potential complications (eg. myocarditis) of even mild infections should be monitored carefully.

The frequency of alcohol, illicit and licit drug consumption in the general driving population in South-East Hungary.

In the framework of the DRUID (Driving under the Influence of Drugs, Alcohol, and Medicines) EU-6 project, a roadside survey was performed in South-East Hungary to determine the incidence of alcohol and the most frequent illicit and licit drug consumption (amphetamines, THC, illicit and medical opiates, cocaine, ketamine, benzodiazepines, zopiclone and zolpidem) in the general driving population. All 3110 drivers stopped between 01 January 2008 and 31 December 2009 were checked for alcohol, and among them 2738 persons (87.7%) participated in the further examinations, on a voluntary basis. Licit and illicit drugs were determined from their oral fluid samples by GC-MS analysis. Illicit drugs were detected in 27 cases (0.99%), licit drugs in 85 cases (3.14%), and alcohol (cut off: 0.1g/l) was found in 4 (0.13%) cases. Illicit drug consumption was the highest among men of the ages 18-34, during the spring, and on the week-end nights. With respect to licit drugs, the highest incidence was found among women over the age of 50, during the summer, and on the week-days. All alcohol positive cases were men over the age of 35. In comparison to international European averages, the alcohol and illicit drug consumption was low, but the licit drug consumption was over the European average.

[Patients' rights of the deceased and related problems in Hungarian law]. / A halottakra vonatkozó betegjogi szabályozás és ennek problémái a magyar jogban.

In the Hungarian law, non-burial interventions on cadavers are regulated only by the health law and, therefore, other scientific examinations are theoretically not allowed. Only the international ethical code of museums is used in certain cases. Numerous cultures consider this practice as the mutilation of the cadaver. Beyond this and the criminal forms of mutilation, the medical interventions (trial and training) are also appropriate to hurt the dignity of the dead. As a counterweight, the consent of the patient or his/her relatives is needed for post-mortem interventions. This study presents the Hungarian legislation in which the deceased is a 'patient', and the special enforcement of patients' rights takes place in relation to the body. The relatives have many rights concerning autopsy, and the anatomy institutes are also regulated. The presumption of opting-out is used for organ harvesting; objection is accepted only from the patient. Medical data of the deceased are strictly protected, but there are no obstacles to the interests of the relatives. Graduate and postgraduate medical education pays only little attention to these issues, and the legislation is not in line with the present expectations and possibilities, so that it would be advisable to reconsider the full spectrum of the problem.

[A new designer drug: methylone related death]. / Új dizájner drog: metilonfogyasztással összefüggo haláleset.

This report presents a fatal case related to the consumption of methylone, a relatively new cathinone type designer drug. A 16-year-old boy suddenly lost his consciousness in a party. Resuscitation had been continued for about 1.5 hours at the intensive care unit, but it was unsuccessful. His previous history included cardiac malformation detected at infancy and bronchial asthma had been diagnosed one year before his death. Signs of sudden cardiac death were observed during autopsy. Methylone intake was proved in blood and liver extract using gas chromatography/mass spectrometry; its concentration was 272 ng/ml in the blood, and 387 ng/g in the liver. Pathohistology revealed microvascular steatosis in the liver, which raised the possibility of chronic use of toxic substances. In addition, striated heart muscle damage was observed, which could be due to the use of an amphetamine-like substance. The authors presume that steatosis of the heart muscle, congenital heart disease and bronchial asthma could be predisposing factors for sudden cardiac death that occurred in the presence of relatively low levels of methylone. Access to various designer drugs is easy, fast and broad. Consequently, the potential abuse or overdose should be taken into consideration in the emergency practice. The use of "non-illicit" drugs does not require formal intervention by the authorities, but the medical service must alarm the stakeholders.

[Traps in detection and post-mortem administration of death in the everyday practice of a clinician]. / Csapdahelyzetek a klinikai orvosok számára a kórházi halálmegállapításban és halottkezelésben.

70% of the death cases in Hungary occur in hospitals, so there is an extraordinary importance of the correct detection of the death, the medical cause of death and the management of the postmortem process. This article presents the obligations of physicians of clinical wards step-by-step, and the insufficiencies and faults experienced several times leading to complaints and pleas from the relatives. Beyond the legal background the specific needs of medical ethics and communication are also presented. Some elements of the final case-summary (epicrisis of the dead), as the complete and complex case-history are described in details. Author suggests a few points of view for renewing the hospital manuals and creating local professional protocols covering the activities of the clinical wards as well as the pathology and administrative units of the hospital, which protocols may act also as quality assurance and lawsuit prevention instruments. The examples of deficient practice are taken from medical experts' experiences and from Hungarian case-law.