Bilateral granulosa cell tumor in a mare.
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Biomedical subjects
Publications and source records attributed to M Manno.
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Routine evaluation of 12 children with Cooley's anemia revealed that each one had a prolonged partial thromboplastin time. However, prothrombin time and thrombin time were within the normal range. Specific assays demonstrated low levels of the four contact factors: factors XI, XII, prekallikrein, and high molecular weight kininogen. Further investigation revealed activity against para-nitroanilide peptide substrates in unactivated plasma from all 12 patients. Following gel filtration on Sephadex G200, the activity emerged in one peak in the void volume, indicating a molecular weight of greater the 500,000. Activity was greatest against H-D-Pro-Phe-Arg-pNA, the substrate for plasma kallikrein, and was inhibited by diisopropyl fluorophosphate and trasolyl. It was unaffected by hirudin, soy bean trypsin inhibitor, and lima bean trypsin inhibitor. It was destroyed by heating at 56 degrees C. Specific antisera against human prekallikrein and human alpha-macroglobulin did not reduce the activity. It is concluded that a high molecular weight kallikrein-like protease, is present in the plasma of these patients. It is postulated that it is released into the circulation from tissue as a result of damage due to iron overload. It is further postulated that this protease brings about in vivo activation of the contrast factors, resulting in a fall in their circulating levels.
The effect of tricresylphosphate (TCP) was studied in vitro and in vivo on the rat liver and brain enzymes acetylcholinesterase (ACC), butyrylcholinesterase (CHE), arylesterase (ARE), aliesterase (ALI), and the microsomal nicotinamide-adenine dinucleotide phosphate oxidase (NADPH2-oxidase) system. The results show that, in the male rat, TCP given intraperitoneally induces an increase in liver microsomal ARE AND NADPH2-oxidase and a decrease in ALI and cholinesterase; no activation of ARE and NADPH2-oxidase is observed in female rats.
Among 1216 workers who were employed in a polyvinyl chloride production factory and who had had no previous dust exposure elsewhere, 20 cases of pneumoconiosis were found. Chest x-ray abnormalities were characterized by limited profusion, irregular type and low gravity. All 20 workers had been exposed to high PVC dust levels. The chest x-ray changes were observed after a minimum exposure of five years and, in a small percentage of cases, were associated with slight restrictive respiratory function impairments. Moreover, in the whole group of workers 388 cases (31.9%) were found with non-specific x-ray abnormalities mainly related to age and smoking.
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This paper aims to discuss the scientific evidence to answer the question in the title. After a brief mention of the fundamental toxicological principles of risk assessment (hazard, exposure, susceptibility, risk), the concepts of dose-response, dose-effect and threshold-dose are presented. The difference between adverse effects with and those without a threshold is highlighted, together with the corresponding methodologies used in risk assessment for the definition of the limit values, i.e. the No Observed Adverse Effect Level (NOAEL) and Safety Factor (SF) method and the Virtually Safe Dose (VSD) method. The two methods correspond to two different types of effect, i.e. deterministic and stochastic, and to two different shapes of the dose-response curve at low doses. The various possible meanings (semantic, toxicological and practical) of the terms "low doses" are discussed: a dose (or concentration) may be low because it does not cause measurable adverse effects (as from Paracelsus' aphorism) or because it is too low to be (analytically) measurable or because it is close to or within the "normal" values of a reference population or because it is well below the exposure limit(s). These various concepts are presented also in relation with the controversial concept of "moderate risk" introduced by a recent Italian legislation (D. Lgs 25/02) on the protection of the workers against chemical risk. It would not be appropriate to set a level of risk simply based on the dose (or the level of exposure) without considering the two other components of risk, i.e. hazard and susceptibility, whose estimation also needs a careful and competent evaluation by the occupational physician. For a thorough discussion of the "moderate risk" concept see a specific paper in these Proceedings. So, clinical, epidemiological and toxicological evidence indicates that in some individuals, groups of the population or circumstances, adverse effects can be observed or expected even at low doses, at which the large majority of the population shows no effect. This is due to a number of factors including toxicological interactions, immunoallergic mechanisms, metabolic hypersusceptibility, both genetic (polymorphism) and acquired (phenotype), preexisting traits or diseases, living habits, diet and others. The Authors conclude therefore that to ensure the protection of all the workers' health and safety, the clinical, toxicological and epidemiological expertise of the occupational physician appears to be fundamental and unreplacable.
This paper describes the position of the Joint Working Group of the Italian Association of Industrial Hygienists (AIDII), the Italian Society of Occupational Health and Industrial Hygiene (SIMLII) and the Italian Society of Toxicology (SITOX) on "Analysis of Parliamentary Act D.Lgs 25/02 and role of the Scientific Societies in the definition of Limit Values". The positive aspects of the new law which implements the European Directive 98/24 are discussed, including the abolition of the rigid periodicity of medical examinations as stated by the old rule D.P.R. 303/56. The Authors also address various parts of the law which appear to be unclear and controversial and highlight the expected difficulties arising for the employers and the safety and health professionals during the application of this new piece of legislation. Moreover, a number of discrepancies are noted between the new Italian law and the original Directive or other current Italian rules such as i. the translation of the term "slight risk", as from the original Directive, into "moderate risk", and the resulting non compulsoriness of health surveillance and biological monitoring of the workers in presence of a "moderate risk", ii. the concurrent exclusion, under the same circumstances, of the occupational physician from risk assessment procedures and iii. the upward modification of the previously established (D.Lgs 277/91) occupational exposure limits for lead. Moreover, the Authors examine and criticize--both in semantic and in toxicological terms--a recent proposal for the definition of "moderate risk" made by an ad hoc Consulting Committee of the Labour Ministry, in which the term "moderate" has been interpreted either as "low" or as "irrelevant for health effects", clearly two very different meanings. Besides, it would be inappropriate to define the conditions of a moderate risk based only on the level of exposure to the chemical (expressed as a fraction of the corresponding limit value), without considering the two other components of risk assessment for that chemical (hazard and susceptibility). Even worse would be the use of simplified models based on "algorithms", which might be useful in a preliminary phase of risk assessment, but easily could lead to an under- or over-estimation of risk, particularly when used by non professionals. In conclusion, the Working Group recommend that the new law be amended in order to clarify its most controversial aspects, whose misinterpretation could severely jeopardize the protection of the workers' safety and health at work.
Biological monitoring or, simply, biomonitoring (BM), refers to the periodic measurement of biological markers, or biomarkers (BMKs), in human fluids and tissues to assess the interaction (absorption, early health effects, susceptibility) between physical, chemical or biological agents and the human organism. The primary aim of BM in the workplace is to integrate environmental monitoring data and detect early, reversible biochemical or functional changes in workers exposed to chemicals before they become clinically relevant. BM also contributes to the assessment of chemical risk to workers, as individuals or as a group. Biomarkers are generally divided into three main types: biomarkers of exposure (BME), response/effect (BMR), and susceptibility (BMS). Other, more specific types of biomarkers are those of internal dose (BID), those of biologically effective dose (BED) and early biomarkers of disease (EBD). It is not always easy, however, to allocate a given BMK--such as the measurement of cytochrome P450 phenotype in subjects exposed to organic solvents--to one or the other type. Biomonitoring provides several advantages over environmental monitoring or health surveillance. For example, it allows an estimate of inter- and intra-individual variability in the absorption, distribution and excretion of chemicals. It also allows the detection of reversible changes before the appearance of a clinically relevant occupational impairment or disease. For these reasons, BM has become a routine procedure in occupational health practice throughout the world. Even the widely acknowledged, recently updated Code of Ethics for Occupational Health Professionals, a milestone in occupational health practice, only provides the basic ethical principles associated with biological monitoring. The aim of the present paper is to survey the various types of BMK available today with two main objectives: to discuss their toxicological significance and highlight the substantial differences that exist between their use in the practice of occupational health and in medical research. The development of new, more valid and reliable BMKs is strongly dependent on the understanding not only of the toxicokinetic and toxicodinamic mechanisms of chemicals, but also of the various susceptibility factors involved, whether genetic or environmental. It is hoped that the concurrent use of BMKs of different types may improve chemical risk assessment in workers, both individually and as a group.
If a society aims at preserving its socio-ethical values, practices concerning the planning, assessment and management of biomonitoring tests in occupational health surveillance and research should not conflict with these values. Protecting both health and employment of every candidate or employee must be the aim of the occupational health physician. For assessing ethical acceptability of occupational health surveillance practices, their accuracy, relevance, need or necessity, and consequences must first be analysed. This analysis must constitute the basis for any societal democratic decision making process, which cannot be substituted for simply by individual informed consent. A physician trained in occupational health is the professionalism required for doing the testing and assuring the protection of the confidentiality of medical data, in accordance with strict legal and deontological rules. In biological monitoring studies and, in general, in any occupational health research settings, however, the principle of individual, really informed consent must be used, whenever possible. This may also considerably contribute to the committment of study subjects to the research goals. On the other hand, this committment would also contribute to promoting impartial research which is needed to improve the knowledge in occupational health and to increase health protection and prevention.
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The curriculum of Italian Medical School of the Faculty of Medicine has been recently renewed at a national level. Considering the numerous innovations introduced, a new role has been attributed to the teaching of occupational health, particularly occupational medicine. Occupational Medicine is usually regarded as a part of community medicine and, despite the fact that occupational disease may be in decline in industrially developed countries, the increasing concern regarding environmental pollution related health effects, stress the relevance of the methodologies already formulated within the occupational health disciplines. Of all environmental factors, occupational medicine has contributed largely to the knowledge about the health effects of occupation and its role in the complex problem at work related to today's medical students as a way of introducing the appreciation of worldwide environmental effects and how to measure, monitor and modify them. In this article the content of the occupational health course is revised and according to the principles of modern medical pedagogy, the teaching is divided in primary and secondary objectives and organized to the resolution of real problems. The importance of the relevant evidences of clinical occupational medicine is discussed and their insertion into other clinical disciplines is proposed. The knowledge of distribution, recognition, management and prevention of the major occupational diseases is a final target of the teaching. The introduction of innovative teaching methods such as factory visits, case history discussion or role playing exercises is suggested as an integrated, multidisciplinary approach able to promote the preventive attitude of students. The efficacy of the teaching has to be evaluated with appropriate methods every time, to verify both informative and formative aspects.
Several pathological processes have been attributed to or associated with free radical mechanisms, including inflammation, cardiac reperfusion injury, aging, and cancer. Moreover, free radicals (FR) produced as reactive intermediates or species during the metabolic activation of an increasing number of industrial chemicals or other toxic agents have been regarded as being primarily responsible for the toxicity of these compounds. Some of the mechanisms involved in FR-induced tissue damage are reviewed, using the following specific examples from occupational medicine: the acute hepatotoxicity of carbon tetrachloride, the delayed lung toxicity of paraquat, the asbestos-induced lung disease, and the carcinogenicity of aromatic amines.
Biotransformation is an important step in the investigation of occupational toxic chemicals. This is because the knowledge of the metabolic pathways and the enzymes involved in the activation and/or detoxication of xenobiotics may help in understanding the mechanism of toxicity and to rationalize the biological monitoring of exposed subjects. The largest enzymatic system involved in the biotransformation of industrial chemicals is cytochrome P-450, a family of haemoproteins capable of metabolizing a vast number of lipophilic, structurally different compounds. The study of the various metabolic reactions of this peculiar group of enzymes has greatly contributed to a) the clarification of the mode of action of several classes of occupational toxic and/or carcinogenic compounds, such as aromatic amines, polycyclic aromatic hydrocarbons, halogenated alkanes, benzene compounds and others, and b) the improvement of risk assessment in the biological monitoring of the exposed subjects, by allowing the toxicological significance (activation/detoxication) of single metabolites to be better understood.
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Studies aided by transmission electron microscopy were made in order to evaluate the occurrence and efficiency of the human follicular fluid in the activation of the processes leading to the acrosome reaction; quantitative, qualitative and morphological data and relative evaluations are here presented. The effects of the human follicular fluid were compared with those determined by other types of treatment, semen untreated, Pellet-Swim-up, and Centrifugation on Discontinuous Percoll Gradient. The transmission electron microscope observations permitted to evaluate the percentage of sperm with an activation of the acrosome reaction in the different groups. The analysis of the data showed a statistically relevant difference (P < 0.001) among the first group (Control group) and the SU group, the MP group and the hFF group, regarding the sperm with AR activation. The sperm treatment with 50% diluted hFF represents an important option to the preparation protocols of the semen samples useful for ART.
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