Correlations between demographics, knowledge, beliefs, and attitudes regarding organ transplantation among academic students in Poland and their potential use in designing society-wide educational campaigns.

BACKGROUND: Family objection precludes 10% of cadaveric donations in Poland. Academic students represent a socially influential demographic group. Educational campaigns improving their attitudes may increase overall donation rates. The aim of this study was to assess correlations between knowledge, beliefs, and attitudes regarding organ transplantation and the identification of the most critical factors affecting one's donation preferences. METHODS: Eight hundred students from 4 public universities in Krakow, Poland, participated in the study; participants were diverse in age, sex, hometown population, and academic discipline (400 medical, 400 non-medical). This cross-sectional study was conducted with the use of a group-administered questionnaire inquiring into demographics, general and professional knowledge, beliefs, and attitudes toward organ transplantation. RESULTS: Attitudes toward organ donation correlate positively with beliefs (ρ = 0.36), general knowledge (ρ = 0.48), and professional knowledge (ρ = 0.23) scores. Beliefs were proven to correlate with general (ρ = 0.21) and professional (ρ = 0.26) knowledge as well. Misconceptions about the medical criteria allowing cadaveric organ recovery, distrust for brain death reliability, fear of "do not resuscitate" approach toward Organ Donor Card holders, a strong belief in organ trafficking, and unawareness of family members' attitudes are the most important factors influencing one's refusal/uncertainty to donate. CONCLUSIONS: Knowledge, attitudes, and refusal rates differ, depending on the academic discipline as well as other demographics, indicating a need for a specifically targeted approach in designing educational campaigns. Sources of knowledge are related to donation rates, with pre-academic education evaluated as unfavorable, as opposed to healthcare providers and the media.

Current state of knowledge, beliefs, and attitudes toward organ transplantation among academic students in Poland and the potential means for altering them.

INTRODUCTION: Students manifest a high level of social commitment. Improving their knowledge and developing more positive attitudes toward organ transplantation may increase the number of organ donations. This study was an assessment of the knowledge and attitudes toward organ transplantation among young people in Poland, with an overview of current beliefs and potential methods for improving transplantology awareness. SUBJECTS AND METHODS: The study included 400 medical students and 400 nonmedical students from public universities in Kraków, Poland. Data were collected by using an anonymous questionnaire examining demographic factors and transplantology issues. RESULTS: Despite the overall positive attitude toward transplantology among academic students in Poland, the state of knowledge of the nonmedical population remains relatively low. The most important issues for social education to focus on are the role of presumed consent and brain death diagnosis, actual hazards of living donations, recipient qualification criteria, and the attitudes of religious authorities. The overall level of knowledge and the number of positive attitudes were significantly higher among medical students than among nonmedical students, proving that formal educational programs are more efficient than the more accessible but less reliable sources of knowledge. CONCLUSIONS: Introduction of transplantology issues in schools and churches, promoting the positive outcomes of organ transplantation rather than negating false beliefs, and eliminating misleading information from the media may significantly increase young people's knowledge and result in more positive attitudes toward transplantology in a society-wide fashion. This outcome could create a favorable background for introducing an opt-in system of consent for organ donation.

Organ Donor Cards--concepts versus reality: a study among academic students in Poland.

INTRODUCTION: Organ Donor Cards (ODCs), despite presenting no legal value in Poland, are considered an important mean of expressing one's intent toward organ donation. This study was an assessment of the effectiveness of ODCs in social communication and their connection to one's transplantology knowledge, attitude, and beliefs. SUBJECTS AND METHODS: The study included 400 medical students and 400 nonmedical students from public universities in Kraków, Poland. Data were collected by using an anonymous questionnaire with attached ODCs examining demographic factors and transplantology issues. RESULTS: Approximately 41% of students possess an ODC, and the majority of the remaining group are willing to sign one. The main reasons for not having an ODC originate from a positive or neutral interest in organ donation (eg, previous conversation with the family, lack of knowledge about ODCs and how to obtain them) rather than a negative one (fear of "do not resuscitate" approach or organ trade) and remain open for modification. Eighty-three percent of ODC holders are aware of its ethical rather than legal value, and 3 of 4 have informed their family about their attitude, proving ODCs are an effective way of expressing one's intent toward organ donation. An actual ODC holder presents a more explicit positive attitude than a potential one, and his or her level of transplantology knowledge is significantly higher. CONCLUSIONS: The support for informed consent for organ donation is particularly strong among students presenting with the highest level of transplantology awareness, with a good/very good state of knowledge and extremely positive attitudes, already owning an ODC, and using it correctly. Thus, such a decision will have the status of a truly conscious and thoroughly considered choice.

Brain death versus irreversible cardiac arrest--the background and consequences of young people's opinions on stating death in Polish transplantology.

BACKGROUND: Brain death and irreversible cardiac arrest (ICA) are legally valid diagnoses obligatory for stating organ donors' death in Poland. Their misinterpretation may affect one's attitude toward organ donation. We assessed young people's knowledge and attitudes toward stating death in transplantology and their impact on attitude toward organ transplantation. METHODS: A total of 400 medical and 400 nonmedical students from public universities in Kraków, Poland, participated. Data were collected with a questionnaire examining demographic factors and transplantologic issues. RESULTS: Brain death diagnosis has a stronger association with stating death in transplantology than ICA, although the level of trust for this diagnosis remains relatively low among nonmedical respondents (38.5% vs 78.5%). Professional knowledge about stating brain death did not correlate with the level of trust for said diagnosis as strongly as it was expected, suggesting the presence of alternate contributing factors, some identified as doubts about brain death criteria (31.5%), distrust for the medical staff's education (25%), and objectivity (20%). CONCLUSIONS: The number of nonpositive attitudes toward organ transplantation was significantly higher among respondents unwilling to accept brain death as the death of a human being, a statement proven to be related to one's opinion about the reliability of said diagnosis, one's awareness of an alternative diagnosis of ICA, and one's general transplantologic knowledge. However, a low number of respondents acknowledging ICA as the only diagnosis valid for stating death of a cadaveric donor (7.6%) suggests that the majority of young Poles are willing to accept brain death as an equally valid, if not more significant, diagnosis.

YKL-40, a novel marker of cardiovascular complications, is related to kidney function in heart transplant recipients.

BACKGROUND: YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesions of atherosclerosis. Elevated serum YKL-40 levels are independently associated with the presence and extent of coronary artery disease and cardiovascular mortality. Because there are no data on heart transplant recipients and because they are prone to cardiovascular complications, the aim of this study was to assess YKL-40 in this population with particular attention to its relationship with endothelial damage. We studied 84 patients after heart transplantation. Healthy volunteers served as control subjects. METHODS: Complete blood count, urea, creatinine, lipids, fasting glucose, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and iron status were studied with the use of standard laboratory methods. We assessed YKL-40, copeptin, markers of inflammation high sensitivity C-reactive protein (hsCRP) and interleukin (IL) 6, and markers of endothelial cell injury von Willebrand factor (vWF) and midkine with the use of commercially available assays. RESULTS: Mean levels of YKL-40, IL-6, vWF, and hsCRP were significantly higher in heart allograft recipients than in the control group (P < .001). In univariate analysis, YKL-40 was related to kidney function (creatinine, r = 0.63 [P < .001]; estimated glomerular filtration rate, r = -0.44 [P < .001]), NT-proBNP (r = 0.45; P < .001), age (r = 0.33; P < .01), time after transplantation (r = 0.23; P < .05), copeptin (r = -0.42; P < .001), soluble transferrin receptor (r = 0.24; P < .05), hemoglobin (r = -0.42; P < .001), transferrin (r = -0.31; P < .01), haptoglobin (r = 0.39; P < .001), cystatin C (r = 0.55; P < .001), ejection fraction (r = -0.28; P < .05), New York Heart Association functional class (r = -0.41; P < .01), hsCRP (r = 0.26; P < .05), IL-6 (r = 0.23; P < .05), vWF (r = -0.40; P < .001), and midkine (r = 0.33; P < .01). In multivariate analysis, only creatinine was found to be a predictor of YKL-40 (ß = 0.59; P = .02), explaining 56% of the variation in YKL-40 levels in heart allograft recipients. CONCLUSIONS: YKL-40 may contribute to the enhanced risk of cardiovascular complications mainly owing to impaired renal function in patients after heart transplantation.

N-nitrosylation potential of mono-N-desethylamiodarone at physiological pH.

Amiodarone (AMI) is frequently used for the treatment of supraventricular arrhythmias. The parent drug is rapidly dealkylated to mono-N-desethylamiodarone (MDEA) and the plasma concentrations of AMI and MDEA are comparable. MDEA is a secondary amine and may thus undergo formation to the corresponding N-nitrosamine in combination with coadministered nitrovasodilators. Previous studies have shown that nitrovasodilators release the vasoactive NO? which may nitrosylate thiol or secondary amine groups in aqueous solutions. Therefore, the nitrosylation potential of MDEA at physiological pH was investigated. N-Nitroso-monodesethylamiodarone (NO-MDEA) was synthesized, characterized and used as a reference product for the detection of the corresponding N-nitrosamine. HPLC and NMR results have shown that the NO-MDEA product is an equilibrium of two configurational isomers (syn and anti). NO-release was generated by sodium nitroprusside (SNP) which was exposed to light. The formation to NO-MDEA was assayed by HPLC-UV. It has been found that MDEA is nitrosylated in the higher nanomolar range and that varying oxygenation of the reaction mixture did not significantly affect the reaction yields. The addition of thiols such as serum albumin (0.6mM), l-cysteine (2.5mM) or N-acetylcysteine (2.5mM) inhibited the NO-MDEA formation indicating that they may prevent N-nitrosamine formation in vivo. However, as S-nitrosothiols may also release NO?, in long term exposure to elevated levels of nitric oxide the nitrosylation of secondary amines may be taken into account.

Metabolism of amiodarone (Part III): identification of rabbit cytochrome P450 isoforms involved in the hydroxylation of mono-N-desethylamiodarone.

1. Amiodarone (AMI) is a potent anti-arrhythmic drug and mono-N-desethylamiodarone (MDEA) is its only known metabolite. It was found recently that in rabbit liver microsomes MDEA was biotransformed to n-3-hydroxybutyl-MDEA (3OH-MDEA). 2. In liver microsomes isolated from the untreated rabbit, the formation of 3OH-MDEA obeyed Michaelis-Menten enzyme kinetics with Km = 6.39 +/- 1.07 microM and Vmax = 0.56 +/- 0.21 nmolmin(-1) mg(-1) protein. 3. Furthermore, (1) among chemicals usually used as inhibitors of cytochrome P450, only midazolam (MDZ), cyclosporin A and ketoconazole inhibited the MDEA hydroxylase activity significantly (>60% inhibition), (2) MDZ, a substrate of CYP3A, inhibited the 30OH-MDEA formation competitively (Ki = 10 +/- 5 microM), (3) the formation rates of 3OH-MDEA correlated positively with those of 1'OH-MDZ (r = 0.81; n = 6), and (4) MDEA hydroxylase activity of microsomes isolated from rabbit rifampicin-induced cultured hepatocytes was 4-fold more active than the control. 4. Since CYP3A6 is mainly induced by rifampicin in rabbit-cultured hepatocytes, the data suggest that this isoform is involved in the biotransformation of MDEA to 3OH-MDEA. 5. Since alpha-naphthoflavone, cimetidine and quinidine also partially inhibited the MDEA hydroxylase activity, it is possible that other CYPs, such as 1A, 2C and 2D, may also be active in the metabolism of amiodarone.

Metabolism of amiodarone. II. High-performance liquid chromatographic assay for mono-N-desethylamiodarone hydroxylation in liver microsomes.

Amiodarone (AMI) is a potent antiarrhythmic drug. In vivo and in vitro, AMI is biotransformed to mono-N-desethylamiodarone (MDEA). Recently, it was observed that MDEA was further hydroxylated to n-3'-hydroxybutyl-MDEA (3'OH-MDEA). The performance of a HPLC-UV assay being developed for the quantification of the new compound was investigated. Liver microsomes isolated from rabbit, rat and human biotransformed MDEA to 3'OH-MDEA. Their estimates of Michaelis-Menten parameters were Km=6.39, 25.2, 19.4 microM; Vmax=560, 54, 17.3 pmol/mg protein/min), respectively. Thus, hydroxylase activity in mammals may be the origin of the species dependence observed in the AMI metabolism.

Metabolism of amiodarone (part I): identification of a new hydroxylated metabolite of amiodarone.

UNLABELLED: Amiodarone (AMI) is a potent antiarrhythmic drug, but its metabolism has not yet been fully documented. Mono-N-desethylamiodarone (MDEA) is its only known metabolite. Our preliminary investigations using rabbit liver microsomes had shown that in vitro AMI was biotransformed to MDEA, and the latter was rapidly further biodegraded to other unknown products. The aim of the present study was to investigate the chemical structure of the biotransformed compound of MDEA. Upon incubation of MDEA with rabbit liver microsomes and NADPH as cofactor, MDEA was biotransformed into three unknown products: X1, X2, and X3. The products were purified using chromatography. The chemical structure of the major product, X1, was investigated in detail. HPLC-ESI-MS revealed that MDEA had been oxygenated. Hydrogen-deuterium exchange experiments showed that the X1 molecule contained one exchangeable hydrogen atom more than its precursor MDEA, indicating that MDEA had been hydroxylated. Further results from ESI-MS/MS analysis indicated that the site of hydroxylation was the n-butyl side chain. NMR analysis (1H NMR, one-dimensional-total correlation spectroscopy, and heteronuclear multiple-bond correlation spectroscopy) established the 3-position (omega-1) of the butyl moiety as the specific carbon atom that is hydroxylated. Rat liver microsomes were also able to catalyze MDEA hydroxylation. Compound X1, as analyzed by HPLC-ESI-MS and ESI-MS/MS, was detected in the liver, heart, lung, and kidney tissue of four rats receiving AMI, suggesting that the hydroxylated MDEA was a secondary metabolite of AMI. CONCLUSION: in mammals, MDEA is hydroxylated to the secondary metabolite of AMI [2-(3-hydroxybutyl)-3-[4-(3-ethylamino-1-oxapropyl)-3,5-diiodobenzoyl]-benzofuran].