A Tissue Distribution Study of Propafenone in an Intentional Fatal Poisoning Case.

Propafenone (PPF) belongs to the class 1C antiarrhythmics and can cause electrocardiogram-associated adverse/toxic effects. Cases of PPF intoxication are rarely investigated. We developed a novel and selective GC-MS/MS method for the determination of PPF and its tissue distribution in an intentional fatal poisoning case, which is applicable to PPF quantification in the range of therapeutic to lethal concentrations in complex post-mortem samples. A simple and effective sample pretreatment was applied to all analyzed samples. PPF was determined without the need for dilution, even in highly complex samples containing a wide range of analyte concentrations. Quantification was performed using the standard addition method, developed and validated according to the ICH M10 guidelines. The obtained results indicated that the PPF concentration in the serum from blood taken while alive, before therapy, was the highest ever reported in the literature. Despite the intensive therapy after the patients' admission, the PPF concentrations in the lungs, spleen, femoral blood and cardiac blood were fatal or abnormally high. On the other hand, the concentrations in the liver and skeletal muscle were lower or approximately the same as observed in cases with therapeutic doses. To the best of our knowledge, the distribution of PPF has not been investigated in fatal intoxication cases and can be helpful in clinical or forensic toxicology.

Unusual concentration of tramadol detected in cadaver in the last stage of decomposition and in fly larvae in the immediate vicinity: case report and literature review.

Determination of the manner and cause of death from skeletal remains is almost always very difficult and can be a challenge for medical examiners. At the end also on skeletal remains, it is possible to assess mechanical, chemical, and thermal injuries, although it can be usually impossible. Possibilities to analyze biological material for the presence of drugs are also limited. The present study describes a case of a homeless man's skeletal remains on which a large number of fly larvae were found. Unusually high concentration of tramadol (TML) in the bone marrow (BM) = 4530 ng/g, muscle (M) = 4020 ng/g, and fly larvae (FL) = 280 ng/g was detected using a validated GC/MS method. In all analyzed samples, caffeine and N-desmethyltramadol (except BM) were qualitatively determined. Autopsy findings and toxicological analyses of the BM suggested that the cause of death could probably be intoxication by TML. It is apparent from the reviewed literature that analysis of TML in the late stages of decomposition of human body is rarely performed. Literature is predominantly focused on animal studies. Thus, TML concentrations analyzed in BM, M, or FL could be found helpful in relation to evaluation of intoxication by this substance. However, the significance of the results obtained in the presented study should be confirmed by further analyses of BM, M, or FL, where TML would be proved in lethal concentration in the blood.

Adaptation and validation of the Hungarian version of Thyroid-Related Patient-Reported Outcome-39 (ThyPro-39) questionnaire: testing factor structure, known-group validity with the comparison of quality of life in Hashimoto's thyroiditis and Graves' disease.

BACKGROUND: Living with autoimmune thyroid disease is a longstanding challenge and can seriously affect the quality of life. We aimed to adapt and validate the Hungarian version of the Thyroid-Related Patient-Reported Outcome-39 (ThyPro-39) questionnaire, test its factor structure, and compare two frequent autoimmune thyroid diseases, Hashimoto's thyroiditis, and Graves' disease. We tested the factor structure of ThyPro-39 with a series of confirmatory factor analyses (CFAs). To examine the validity of ThyPro-39 and to compare the quality of life of the two groups - Hashimoto's thyroiditis (N = 240), Graves' disease (N = 51) - CFA with covariates were used. RESULTS: Our results supported a bifactor model with psychosocial and somatic symptoms as general factors, and 12 symptom-specific factors. Based on the analysis of omega hierarchical indices ranging between 0.22 and 0.66, the specific scales also carry information besides the composite scores and should be used when a more detailed analysis is required. In the multivariate analysis, perceived stress was significantly associated with the general psychosocial factor (ß = 0.80), symptom factors (ß = 0.34), anxiety (ß = 0.43), depressivity (ß = 0.37), and emotional susceptibility (ß = 0.38) specific factors. Graves' patients reported more eye symptoms (d = 0.45) and cosmetic complaints (d = 0.40), while Hashimoto patients had more cognitive problems (d = 0.36) and more severe hypothyroid symptoms (d = 0.35). These group differences confirm the known-group validity of the questionnaire. CONCLUSIONS: The validity of the Hungarian version of ThyPRO-39 is supported. We recommend using two composite scores of psychosocial and somatic symptoms and the specific symptoms scores to measure the quality of life in clinical practice and research.

Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity.

Biologically active taxanes, present in small- to medium-sized evergreen conifers of various Taxus species, are widely used for their antioxidant, antimicrobial and anti-inflammatory effects, but mostly for their antitumour effects used in the treatment of solid tumours of the breast, ovary, lung, bladder, prostate, oesophagus and melanoma. More of the substances found in Taxus plant extracts have medical potential. Therefore, at the beginning of this review, we describe the methods of isolation, identification and determination of taxanes in different plant parts. One of the most important taxanes is paclitaxel, for which we summarize the pharmacokinetic parameters of its different formulations. We also describe toxicological risks during clinical therapy such as hypersensitivity, neurotoxicity, gastrointestinal, cardiovascular, haematological, skin and renal toxicity and toxicity to the respiratory system. Since the effect of the drug-form PTX is enhanced by various Taxus spp. extracts, we summarize published clinical intoxications and all fatal poisonings for the Taxus baccata plant. This showed that, despite their significant use in anticancer treatment, attention should also be focused on the risk of fatal intoxication due to ingestion of extracts from these plants, which are commonly found in our surroundings.

Simultaneous analysis of carbohydrates, polyols and amines in urine samples using chemical ionization gas chromatography with tandem mass spectrometry.

A simple method for the simultaneous derivatization of carbohydrates, polyols, amines and amino acids using hexamethyldisilazane and N,O-bis(trimethylsilyl)trifluoroacetamide was developed. This method allows the direct derivatization of urine samples without sample pretreatment before derivatization. The method was successfully used for analysis of the selected metabolites in urine samples of healthy individuals and neonates suffering from galactosemia. The limits of detection by positive chemical ionization gas chromatography with tandem mass spectrometry analysis were in the range of 1.0 mgL-1 for mannitol to 4.7 mg/L for glucose.

Gas chromatography with mass spectrometry analysis of phosphoserine, phosphoethanolamine, phosphoglycerol, and phosphate.

A new, rapid, sensitive, robust, and reliable method has been developed for the qualitative analysis of phosphoserine, phosphoethanolamine, phosphoglycerol, and phosphate using gas chromatography with mass spectrometry and two-step trimethylsilylation. The method employs hexamethyldisilazane for silylation of the phosphate and hydroxyl groups in the first phase and bis(trimethylsilyl)trifluoroacetamide for silylation of the less-reactive amino groups in the second phase. This order is of key importance for the method because of the different reactivities of the two reagents and the mechanism of derivatization of the active groups of the analytes. Trimethylsilylated derivatives of the analytes were identified on the basis of their retention times and mass spectra. The probable structures of the major fragments were identified in the spectra of the trimethylsilylated derivatives and characteristic m/z fragments were selected for each analyte. Fragments with m/z 73 and 299 occurred in the spectra of all the analytes. The characteristic retention data were employed to calculate the retention indices of the individual silylated phosphorylated substances in the hydrocarbon range C12-C19 for the DB-5ms column. The method was employed to measure the polar fraction of the hydrolysate of the cytoplasmic membrane of Bacillus subtilis. The detection limits vary between 5 µg/mL (trimethylsilylated phosphate) and 72 µg/mL (trimethylsilylated phosphoethanolamine).

The analysis of linear and monomethylalkanes in exhaled breath samples by GC×GC-FID and GC-MS/MS.

A new arrangement of the INCAT (inside needle capillary adsorption trap) device with Carbopack X and Carboxen 1000 as sorbent materials was applied for sampling, preconcentration and injection of C6C19n-alkanes and their monomethyl analogs in exhaled breath samples. For the analysis both GC-MS/MS and GC×GC-FID techniques were used. Identification of the analytes was based on standards, measured retention indices and selective SRM transitions of the individual isomers. The GC-MS/MS detection limits were in the range from 2.1 pg for n-tetradecane to 86 pg for 5-methyloctadecane. The GC×GC-FID detection limits ranged from 19 pg for n-dodecane to 110 pg for 3-methyloctane.

Direct silylation of Trypanosoma brucei metabolites in aqueous samples and their GC-MS/MS analysis.

A simple two-step method for the derivatization of polar compounds (lactate, alanine, glycerol, succinate and glucose) using hexamethyldisilazane (HMDS) and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) was developed. This method allows direct derivatization of aqueous samples wihout sample pretreatment. The method was used for the analysis of the metabolites of the unicellular organism Trypanosoma brucei. The limits of detection by GC-MS/MS analysis were in the range of 0.02 mg L(-1) for glucose to 0.85 mg L(-1) for lactate.

Depressive symptoms amongst asthmatic children's caregivers.

We wanted to find out, whether the number of depressive symptoms is higher amongst asthmatic children's caregivers, compared to international data, to the Hungarian population average, and to parents of children with chronic renal disease. Are these depressive symptoms connected to the children's psychological status, asthma severity or current asthma symptoms? One-hundred and eight, 7- to 17-yr-old asthmatic children were enrolled, who have been treated at the Semmelweis University, First Department of Pediatrics. Children were suffering from asthma for at least 1 yr, with a median of 8 yr (1-16 yr), they started to develop asthmatic symptoms between the age of 0.5-14 yr (median: 3 yr). We also identified 27 children with chronic renal diseases and their caregivers, who functioned as a control group. Children were asked to complete the Hungarian-validated versions of the Child Depression Inventory, the Spielberger State Anxiety Inventory for Children and the Juniper Pediatric Asthma Quality of Life Questionnaire. Asthma severity and current symptoms were also documented, 56% had no symptoms on the preceding week. Caregivers were asked to complete the Hungarian versions of the Beck Depression Inventory (BDI) short form, the Spielberger Anxiety Inventory and the Juniper Pediatric Asthma Caregivers' Quality of Life Questionnaire. Caregivers of asthmatic children had significantly more depressive symptoms (7.73 +/- 6.69 s.d.) than the age-specific normal population (p < 0.01). Caregivers of renal patients also experience more depressive symptoms (9.61 +/- 7.43 s.d.) than their healthy peers, but difference between the two chronic diseases' group did not prove to be significant. Asthmatic children's caregivers who scored more points on the BDI than the population average suffer from more anxiety symptoms, but their quality of life is not worse than the caregivers' with less depressive points. Depressive symptoms were neither connected to the children's psychological and asthmatic symptoms nor quality of life. Amongst caregivers of asthmatic children, at least mild depressive symptoms were represented amongst 39% of men and 33% of women. Gender difference was not significant, despite observations in the normal Hungarian population. Amongst caregivers of renal patients, depressive symptoms were represented in 14% of men and 50% of women. Gender difference was significant. (p = 0.05). Significant difference was observed between male asthmatic and renal caregivers, albeit difference was not significant between the female groups. No difference was found in depressive symptoms according to caregivers' level of education. Caregivers of children with asthma have more depressive symptoms than the average Hungarian population, but their results do not differ from caregivers taking care of children with chronic renal diseases. Caregivers of asthmatic children having at least mild depressive symptoms tend to have higher anxiety symptoms as well. Up to date, childhood chronic disease management and long-term care should also focus on parental psychology, mainly on depression and anxiety, as prevalence is higher than in the average population.

[Depression, anxiety and quality of life in pediatric asthma]. / Depresszió, szorongás, életminoség gyermekkori asztmában.

AIMS: The study's objective was to examine depression, anxiety and quality of life according to age and asthma status in pediatric asthma in a pediatric university department. METHODS: 108 patients, age: 11.75 +/- 3.10 (mean +/- SD) years (boys 11.6 +/- 2.8 years and girls 12.1 +/- 3.7 years) completed the Child Depression Inventory, the State Trait Anxiety Inventory for Children, the Pediatric Asthma Quality of Life Questionnaire, and a symptom score. Forced expiratory volume in one second was also measured. RESULTS: Mean forced expiratory volume in one second percent was 97.4 +/- 12.8. 23 patients (21%) had intermittent asthma, 40 patients (37%) had mild persistent, 43 patients (40%) had moderate persistent, 2 patients (2%) had severe persistent asthma. Pediatric asthma patients scored 9.36 +/- 5.57 points in the depression questionnaire. Patients showed as many depressive symptoms as the Hungarian average population, pre-adolescent boys with asthma showed even less. Children with asthma scored 31.16 +/- 4.61 points on the anxiety questionnaire; (boys 30.64 +/- 4.29, girls 32.67 +/- 5.27). Children with asthma have the same anxiety level as their healthy peers. On the quality of life questionnaire asthmatic children reached 6.18 +/- 1.00 (2.87-7.00); adolescent girls scored the worst (5.62 +/- 1.28). Adolescent asthmatic girls have the worst quality of life. Boys reach better quality of life scores as they grow older ( p = 0.02). Girls with adolescence have a tendency of decreasing quality of life, although the difference is not significant. In adolescence, asthmatic girls experience more quality of life deprivation than boys ( p = 0.013). Depression score, anxiety, or quality of life showed no difference between the intermittent and persistent asthmatic groups. Children in the symptomatic subgroup experienced poorer quality of life. Depression and anxiety were not affected by current asthma symptoms. There was no significant difference in depression, anxiety or quality of life scores according to age. CONCLUSION: The psychological status of children with asthma is fairly good. One should concentrate more on the quality of life of girls in adolescence. The good pediatric care of childhood asthmatics helps to avoid the psychological consequences of the disease.

Bronchial asthma and the short-term quality of life: follow-up study of childhood bronchial asthma in Hungary.

The aim of our study is to determine and describe the current short-term health-related quality of life of recent adult patients who had bronchial asthma in childhood. Our objective was to investigate if symptom control in bronchial asthma could be in conflict with general quality of life. We made a follow-up study of 152 patients (105 male, 47 female) over the age of 30 (31-55 yr) who were allergic asthmatics in childhood. The patients' current symptoms and short-term quality of life were evaluated by a questionnaire. The patients developed asthmatic symptoms by age 4.4 (0.5-13) years on the average. Now 60% (91 persons) have no symptoms. They became symptom-free between 3 and 41 yr of age (mean = 14.2 +/- 8.2). Amongst the currently asthmatic patients (58 patients, 38%), 34 patients (22%) belong to the Global Initiative for Asthma (GINA) I, nine patients (6%) to the GINA II, five patients (3.3%) to the GINA III, and five patients (3.3%) to the GINA IV classification. Five patients (3.3%) did not specify their own symptoms. Three persons (2%) did not answer this question. Symptomatic patients reached 5.28 on the Juniper Asthma Quality of Life Questionnaire, while their asymptomatic peers scored statistically higher with 6.8 on the scale. Amongst the symptomatic patients, the most limited areas were: 'bothered by heavy breathing', 'had to avoid a situation or environment because of dust', 'experienced difficulty breathing out as a result of asthma', 'experienced asthma symptoms as a result of the weather or air pollution outside'. They were least 'concerned about medication', 'frustrated as a result of their asthma', they were least limited in 'going outside because of the weather or air pollution'. The most problematic areas for the symptom-free patients were 'had to avoid a situation or environment because of dust', 'had to avoid a situation or environment because of cigarette smoke', 'experiencing asthma symptoms as a result of being exposed to dust and the 'need to clear throat'. It seems that having no asthma symptoms is not equal to having a good quality of life for asthmatic patients. Moreover, symptom control in bronchial asthma is in conflict with quality of life, as many prophylactic measures to prevent exposure to allergens also restrict the patient's life.