Biomedical subjects
Publications and source records attributed to A Forni.
The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 202-208, . The duplicate article has therefore been withdrawn.
Amyloid peptides (Abeta) can operate as volume transmission (VT) signals since they are continuously released from cells of the central nervous system and diffuse in the extra-cellular space of the brain. They have both regulatory and trophic functions on cellular networks. In agreement with Abeta regulatory actions on glial-neuronal networks, the present paper reports new findings demonstrating that intrastriatal injections of Abeta peptides reduce striatal tyrosine hydroxylase, increase striatal GFAP immunoreactivities and lower pain threshold in experimental rats. Furthermore, it has been demonstrated that exogenous homocysteine (Hcy) binds Abeta(1-40) favouring its beta-sheet conformation both in vitro and in vivo and hence the formation of beta-fibrils and development of neurotoxicity. Thus, the hypothesis is discussed that Abeta peptides represent crucial VT-signals in the brain and their action is altered by dysmetabolic signals such as high Hcy extra-cellular levels, known to be an important risk factor for Alzheimer's disease.
AIM: To evaluate safety and efficacy of blood cardioplegia in a retrospective selected (but not randomized) donor/recipient population as standard organ preservation technique in high-risk heart transplants (HTX). MATERIALS AND METHODS: The rationale of different strategies was based on both donor and recipient evaluations. Unstable donors with a long history of well-known risk factors and/or long-distance retrieval were given blood cardioplegia, particularly for HTX candidates in poor preoperative clinical condition. Organ protection was performed by administration of St Thomas II crystalloid cardioplegia in 74 patients (group 1) while 58 others (group 2) received blood cardioplegia. RESULTS: Groups I versus II shows comparable results for immediate postoperative mortality rates (4% vs 7%, P =.4), high doses of inotropic drug support (48% vs 20%, P =.08), and the need for postoperative mechanical assistance devices (9% vs 4.5%, P =.4). In contrast statistically significant differences were observed for occurrence of acute right ventricular failure (50% vs 5%; P =.004), atrioventricular conduction disturbances (63% vs 10%, P =.003), spontaneous sinus rhythm recovery (18% vs 64% P =.0038) and reperfusion interval (RI) (time between removal of aortic cross-clamp and discontinuation of extracorporeal circulation (ECC)) exceeding 30 minutes (70% vs 21%, P =.0004). Higher peak creatine kinase MB mean value (176 +/- 23 vs 90 +/- 19, P =.06) indicated more severe ischemic damage among G1 patients. CONCLUSION: This study suggests that high-risk heart transplant candidates benefit from blood cardioplegia, due to the reduced incidence of both right ventricular failure and severe cardiac arrhythmia. Potential limitations to this novel technique may be linked to the higher expenses due to the need for a perfusion technician. Improved myocardial protection can be seen even in a longitudinal study on chronic rejection: this form of allograft protection may preserve the matrix and the endothelium.
Our study was undertaken to assess the prognostic significance of pharmacological stress echocardiography in 325 diabetic patients. Pharmacological stress echocardiography was performed for diagnosis of coronary artery disease in 128 patients, and for risk stratification in 197 patients. Follow-up was 34 months. Cardiac-related death and non-fatal myocardial infarction were considered hard events. During the follow-up period, there were 38 deaths and 23 acute non-fatal myocardial infarctions. By univariate analysis, a pharmacological stress echocardiography positive response for ischaemia indicated an increased risk of cardiovascular death. However, by multivariate analysis, advanced age and peak ejection fraction <40% were the only independent predictors of cardiac death. The same peak ejection fraction (EF) <40%, rest wall motion score index and previous myocardial infarction were independent predictors of hard events. After dividing the population into two subgroups on the basis of EF at rest, only a peak EF <40% and a pharmacological stress echocardiography positive test were powerful independent predictors of cardiovascular mortality.
A 69-year-old male heart transplant recipient, being treated with Cell Cept, FK 506 and methylprednisolone had multiple deep brown skin nodules and nodes, on the upper right arm. Skin biopsy and culture detected a strain of Curvularia lunata. The infection disseminated to the whole skin surface, oral mucosa, upper third of the oesophagus and to the lungs. Therapy with antibiotics and antifungal drugs was ineffective. The patient died of sepsis. We did not find any other case of systemic dissemination from a skin infection due to C. lunata among heart transplant recipients. We feel that heart transplant recipients need adequate education to prevent situations that would put them at risk for infection and to seek medical advice immediately for an early diagnosis and an effective therapy.
The paper presents the exposure assessment method and quality control procedure used in an international, multi-centre case-control study within a joint Nordic and Italian cohort. This study was conducted to evaluate whether occupational exposure to carcinogens influenced the predictivity of high frequency of chromosomal aberrations (CA) in peripheral lymphocytes for increased cancer risk. Occupational hygienists assessed exposures in each participating country: Denmark, Finland, Italy, Norway and Sweden. The exposure status to a carcinogen or a clastogen was coded in the cohort according to the original CA studies at the time of CA testing, but not for the whole work life. An independent occupational hygienist coordinated harmonization of the assessment criteria and the quality control procedure. The reliability of the exposure assessments was calculated as deviation from the majority of the assessors, as Cohen's kappa and as overall proportion of the agreements. The reassessment of the exposures changed the exposure statuses significantly, when compared with the original cohort. Harmonization of the exposure criteria increased the conformity of the assessments. The prevalence of exposure was higher among the original assessors (the assessor from the same country as the subject) than the average prevalence assessed by the other four in the quality control round. The original assessors classified more job situations as exposed than the others. Several reasons for this are plausible: real country-specific differences, differences in information available to the home assessor and the others and misunderstandings or difficulties in translation of information. To ensure the consistency of exposure assessments in international retrospective case-control studies it is important to have a well-planned study protocol. Due to country-specific environments a hygienist from each participating country is necessary. A quality control study is recommended, to be performed as described, combined with round-table meetings to minimize information bias between the assessors.
A regioregular head-to-head/ tail-to-tail poly(beta,beta'-disubstituted bithiophene) P1 was synthesised by chemical and electrochemical polymerisation of 2,2'-bithiophene that bears (S)-2-methylbutylsulfanyl chains in the beta and beta'-positions. The polymer was characterised by GPC, NMR and UV/Vis spectroscopy, CD, AFM and by electrochemical and conductivity measurements. The CD spectra of P1 in solutions in which poor solvents are present show interesting features and allow the presence of different optically active species to be distinguished. Upon varying the casting conditions of P1, different relative amounts of grainy and homogeneous aggregated phases were observed in AFM micrographies of films and corresponding negative or positive first Cotton effects were found in the CD spectra. AFM, CD and UV/Vis characterisations were also performed on an electrogenerated optically active polymer PE1, in order to make a comparison with the chemically synthesised one. The interesting, small band gap of P1 allows for easy p- and n-electrochemical doping.
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An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role played by exposure to carcinogens is still uncertain because of the requisite information concerning occupation and lifestyle was lacking. We evaluated in the present study whether CAs predicted cancer because they were the result of past exposure to carcinogens or because they were an intermediate end point in the pathway leading to disease. A nested case-control study was performed on 93 incident cancer cases and 62 deceased cancer cases coming from two prospective cohort studies performed in Nordic countries (Denmark, Finland, Norway, and Sweden) and Italy. For each case, four controls matched by country, sex, year of birth, and year of CA test were randomly selected. Occupational exposure and smoking habit were assessed by a collaborative group of occupational hygienists. Logistic regression models indicated a statistically significant increase in risk for subjects with a high level of CAs compared to those with a low level in the Nordic cohort (odds ratio, 2.35; 95% confidence interval, 1.31-4.23) and in the Italian cohort (odds ratio, 2.66; 95% confidence interval, 1.26-5.62). These estimates were not affected by the inclusion of occupational exposure level and smoking habit in the regression model. The risk for high versus low levels of CAs was similar in subjects heavily exposed to carcinogens and in those who had never, to their knowledge, been exposed to any major carcinogenic agent during their lifetime, supporting the idea that chromosome damage itself is involved in the pathway to cancer. The results have important ramifications for the understanding of the role played by sporadic chromosome damage for the origin of neoplasia-associated CAs.
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The present study has the aim of evaluating gene-environment interaction on the levels of different biomarkers in coke-oven workers exposed to PAH. In order to assess whether the levels of some biomarkers (PAH-DNA adducts, nitro-PAH adducts to Hb and MN frequency) could be modulated by the genetic metabolic polymorphisms for CYP1A1 and GSTM1, we analysed in 76 coke-oven workers and 18 controls the CYP1A1 (MspI and Ile/Val sites) and the GSTM1 genotypes by a PCR assay. In individuals with shared setup of CYP1A1 or GSTM1 genotypes, we analysed how the specified biomarkers correlated with total PAH exposure (urinary levels of 1-hydroxypyrene) both by a stratified analysis and logistic regression modelling. Statistically significant (P = 0.03 and P = 0.01) higher percentages of the more susceptible GSTM1- subjects compared to the GSTM1+ subjects and of the more susceptible CYP1A1 Ile/Val individuals compared to the CYP1A1 Ile/Ile individuals were detected for high levels of PAH-DNA adducts in the high exposure group (namely high levels of 1-OHP). A statistically significant association was observed between increased PAH-DNA adduct levels and the more susceptible GSTM1- genotype (P.O.R. = 4.18, P = 0.03) in a logistic regression modelling and a significant interaction between PAH exposure and GSTM1-genotype was found for PAH-DNA adducts. No effect of these metabolic genotypes was observed for MN frequency and nitro-PAH adducts to Hb. In conclusion, a gene-environment interaction between PAH exposure and two metabolic genotypes involved in activation (CYP1A1) and detoxification (GSTM1) of PAHs, respectively, has been identified.
OBJECTIVE: To assess the safety and efficacy of myocardial protection of the donor heart during transplantation with the use of blood cardioplegia, a prospective randomized clinical trial was undertaken between January 1997 and March 1998. METHODS: Forty-seven consecutive patients were assigned either to crystalloid (27 patients; group 1) or blood cardioplegia (20 patients; group 2). Comparison of recipient age (54 +/- 11 years vs 55 +/- 7 years; P =. 9), sex (89% vs 90% male patients; P =.9), diagnosis (63% vs 65% dilated cardiomyopathy; P =.8), elevated pulmonary vascular resistance (30% vs 30%; P =.9), prior cardiac operations (22% vs 30%; P =.5), need for urgent heart transplantation (7% vs 20%; P =. 2), donor age (32 +/- 11 years vs 31 +/- 13 years; P =.7), cause of death (33% vs 40% vascular; P =.5), and global myocardial ischemia (176 +/- 51 minutes vs 180 +/- 58 minutes; P =.5) showed no difference. Hemodynamically unstable donors (15% vs 45%; P =.02) were more prevalent in group 2. RESULTS: Operative mortality rates (4% vs 5%; P =.8), high-dose inotropic support (41% vs 30%; P = 0.6), and postoperative mechanical assistance (11% vs 10%; P = 0.9) were comparable in the 2 groups. Prevalence of acute right heart failure (27% vs 0; P =.02) and of temporary complete atrioventricular block (52% vs 20%; P =.02) were greater in group 1. Spontaneous sinus rhythm recovery was more prevalent in group 2 (11% vs 40%; P =.02). Higher peak creatine kinase (1429 +/- 725 u/L vs 868 +/- 466 u/L; P =.01) and creatine kinase MB (144 +/- 90 u/L vs 102 +/- 59 u/L; P =. 06) levels suggested more severe ischemic injury in group I. CONCLUSION: Use of blood cardioplegia was associated with a lower prevalence of right heart failure, cardiac rhythm dysfunction, and laboratory evidence of ischemia.
BACKGROUND: Instability in the organization and expression of the genetic material has been hypothesized as the basic mechanism of ageing. OBJECTIVE: To quantify the effect of ageing on chromosomal damage as measured by spontaneous micronuclei (MN) frequency in peripheral blood lymphocytes. METHOD: Analysis of a large population sample from two laboratories applying the cytokinesis-block technique and a third using traditional interphase analysis. The age-related effect on baseline level of micronuclei frequency and on cell proliferation measures was further investigated in a study of peripheral blood samples from healthy subjects. RESULTS: There was an increase of MN frequency with age. The regression lines showed a positive slope and were statistically significant (P< 0.01) with a steeper trend for cytochalasin B-treated samples. An inverse correlation with age was detected for the percentage of binucleated cells in laboratories using cytochalasin B. This study confirms the increase of basal level of MN with age. A decrease by age in proliferation efficiency measured by the percentage of binucleated cells suggests an interference of age-related factors on cell division. CONCLUSION: There is an increase in MN frequency with increasing age.
The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.
It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated cohorts, forming a joint study base of 5271 subjects, will now be performed, allowing a more solid evaluation. The importance of potential effect modifiers, such as gender, age at testing, and time since testing, will be evaluated using Poisson regression models. Two other potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.
The incidence of tuberculosis (TB) worldwide is currently on the rise, not only in the general population but also quite notably among immunosuppressed patients. Its incidence among patients undergoing antirejection therapy is considerably higher than in the general population, and heart transplant recipients have been found to carry the highest risk of TB. There are no reported data, however, on primary TB caused by multidrug-resistant (MDR) Mycobacterium tuberculosis (M. tuberculosis) in heart transplant recipients. We describe the case of a patient who developed active primary MDR TB following the reactivation of a latent tuberculous infection 6 months after transplantation. The patient was most likely infected by M. tuberculosis during a period of time he spent in prison 10 years before undergoing transplantation, but he never developed active tuberculosis, nor did he ever receive antituberculous medication prior to transplantation. Because of the atypical clinical presentation, establishment of the diagnosis was postponed, and the resistance pattern of the isolate grown from bronchoalveolar lavage (BAL) specimens (resistant to isoniazid and rifampicin) led to treatment failure and a fatal outcome. The adoption of the most rapid diagnostic tools for the identification of M. tuberculosis and for a quick screening of drug-resistant isolates is urgently needed in those centers where organ transplantation is carried out.