[Evaluation of outpatient medical pain management in Germany : Results of an internet-based cross-sectional survey among pain specialists in outpatient departments]. / Bewertung der ambulanten ärztlichen Schmerztherapie in Deutschland : Ergebnisse einer internetbasierten Querschnittsbefragung unter ambulant tätigen Schmerzmedizinern.

BACKGROUND: On 31 December 2016, a total of 1206 physicians participated in the outpatient care of chronic pain patients according to the criteria of a special pain management program (QSV). Because of the largely existing shortage of treatment resources for chronic pain patients, there is a lack of data regarding the evaluation of outpatient pain management by highly specialized pain therapists. METHODS: In a hybrid Delphi procedure, a questionnaire concerning the content, structural and personal assessment of outpatient pain management in Germany was developed. With the help of this instrument, an internet-based cross-sectional survey of 281 QSV pain therapists from four German states (Berlin, Lower Saxony, Saxony, Baden-Württemberg) and of all the heads of university outpatient pain services (n = 36) in Germany was conducted. RESULTS: The adjusted response rate of the survey was 35.9%. The response rate of the heads of university outpatient pain services was 66.7%. In 91% of the respondents the proportion of chronic pain patients in the medical practices was more than 70%. Whereas 67.3% were satisfied with the situation in their medical practice, 63.4% were dissatisfied with the current organizational structure of the pain management in Germany. They expressed their dissatisfaction especially in terms of budgeting regulations (69.3%), the cooperation with psychotherapists (69.3%) and interdisciplinary networking (50.5%). The 1­year specialist training in pain management (87.1%) and the completion of a psychosomatic basic care course (90.1%) were assessed as a good preparation for the later profession. A multitude of free comments indicated that the pain specialist training is too short and insufficient. Most of the respondents considered the establishment of a specialist board certification for pain management more suitable from the perspective of physicians (61.4%) and the patients (54.5%). Of the heads of university outpatient pain services 70.8% expressed the wish for autonomous structures with separate budgets and 75.0% indicated that under the current conditions their outpatient pain services are not working profitably. Only 39.7% of the QSV pain therapists provided fellowship training for physicians and 57.6% were planning to retire during the next 10 years. CONCLUSION: Highly specialized pain therapists are dissatisfied because of the lack of independence of the organizational structure of pain management care and the insufficient interdisciplinary network in outpatient pain management. A possible solution for a better pain management care and the recruitment problems may be the establishment of a board certification for pain management.

[Erythromelalgia: skin redness and pain]. / Erythromelalgie: rote Haut und Schmerz.

Erythromelalgia is a rare disease that is associated with hemato-oncological diseases or after taking certain drugs and toxins, but it can also occur as an independent clinical picture, for example, due to mutations in the sodium channel NaV1.7. Clinically, there is a characteristic triad of attack-like burning pain and skin redness in the area of the distal extremities, which can be alleviated by excessive cooling. The attacks are triggered by heat, exertion, and stress. The diagnosis is primarily made clinically and can be confirmed by genetic testing if a sodium channel NaV1.7 mutation is present. Important differential diagnoses are complex regional pain syndrome, the non-freezing cold injury, and small fiber neuropathies. Therapy is multidisciplinary and has to be planned individually and include physical therapy and psychotherapy as well as drug therapy as integral components.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.

OBJECTIVES: Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. METHODS: An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30 min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. RESULTS: LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228 ± 8.5 ms, vs. 181 ± 3.6 ms, p < 0.01) and LEP amplitudes were reduced (14.8 ± 1.2 µV vs. 24.6 ± 1.7 µV, p < 0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649 ms vs. 427 ms, p < 0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p < 0.01). CONCLUSION: The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept that A-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors.

Mechano-sensitive nociceptors are required to detect heat pain thresholds and cowhage itch in human skin.

BACKGROUND: Mechano-sensitive and mechano-insensitive C-nociceptors in human skin differ in receptive field sizes and electrical excitation thresholds, but their distinct functional roles are yet unclear. METHODS: After blocking the lateral femoral cutaneous nerve (NCFL) in eight healthy male subjects (3-mL Naropin(®) 1%), we mapped the skin innervation territory being anaesthetic to mechanical pin prick but sensitive to painful transcutaneous electrical stimuli. Such 'differentially anaesthetic zones' indicated that the functional innervation with mechano-sensitive nociceptors was absent but the innervation with mechano-insensitive nociceptors remained intact. In these areas, we explored heat pain thresholds, low pH-induced pain, cowhage- and histamine-induced itch, and axon reflex flare. RESULTS: In differentially anaesthetic skin, heat pain thresholds were above the cut-off of 50°C (non-anaesthetized skin 47 ± 0.4°C). Pain ratings to 30 µL pH 4 injections were reduced compared to non-anaesthetized skin (48 ± 9 vs. 79 ± 6 VAS; p < 0.01). The axon reflex flare area did not differ between these zones (7.8 ± 1.4 cm(2) vs. 8.3 ± 0.5 cm(2) ). Histamine iontophoresis still caused pruritus in differentially anaesthetized skin in five of eight subjects (VAS 26 ± 14), whereas itch upon cowhage spicules was absent (VAS 0 vs. 29 ± 11 in non-anaesthetized skin). CONCLUSIONS: We conclude that activation of mechano-insensitive nociceptors is sufficient to provoke itch by histamine- and acid-induced pain. The mechano-sensitive nociceptors are crucial for cowhage-induced itch and for the assessment of heat pain thresholds.

[Cross-sectional subject 14--training in pain]. / Querschnittsfach 14--Lehre zum Thema Schmerz.

The introduction of pain medicine (cross-sectional subject 14, QF 14) into the Human Medicine study program is a great opportunity. A knowledge gap concerning the treatment of pain patients outside of specialized pain centers has been recognized for many years. This gap might be closed or at least reduced by a compulsory curriculum in pain medicine. If implementation of new lessons for QF 14 is not possible, pain medicine could be represented by labelled elements in the existing curriculum, in order to highlight the field. The core curriculum must now be converted into appropriate teaching and test formats. Due to the autonomy and heterogeneity of German medical faculties, no uniform solution will be achieved. In contrast, this diversity and the entirely new implementation of the cross-sectional subject will allow structured evaluation of different teaching and examination formats with respect to teaching outcome in benchmarking investigations in the coming semesters. Practically experienced lecturers and theory-driven medical educationalists are called upon to get involved with the development, implementation, and evaluation of pain medicine in undergraduate education in Germany. Teaching enthusiasts are encouraged to dedicate themselves to the strenuous, but stimulating task of implementing QF 14. The Deutsche Schmerzgesellschaft (German Pain Society) will offer support for this.

[Medical educational evaluation of the German Pain Congress 2012. In the context of the CanMEDS physician competency framework]. / Deutscher Schmerzkongress 2012 aus medizindidaktischer Sicht. Bewertung unter Berücksichtigung der im Rahmenmodell CanMEDS definierten Arztrollen.

BACKGROUND: Professionals in the medical field are expected to participate in continuing medical education in the sense of lifelong learning. The authors took this occasion to evaluate the most important national convention in pain medicine concerning its role in medical education. MATERIAL AND METHODS: The participants of the 37th German Pain Congress (17-20 October 2012 in Mannheim) were asked to complete a questionnaire concerning content and design of the convention. The aim of this study was to analyze the distribution of different physician competencies in the program. For this purpose the congress program was analyzed with respect to the various medical role models as defined in the Canadian medical education directions for specialists (CanMEDS) framework. RESULTS: The participants considered the quality of the different sessions of the German Pain Congress to be good. The poster sessions were considered to be the second most important educational format in the congress following the live sessions. Concerning the content of the congress the participants wished more emphasis on the role of interprofessional partners, such as nursing and psychotherapy. The CanMEDS physician roles of manager, communicator, health advisor and professional paragon were underrepresented in the congress program in this study. CONCLUSION: Regarding content and educational value, the congress design could benefit from additional Praktikerseminaren (practical seminars). The role of interprofessional partners should be more emphasized. In addition the program could become more attractive through a more balanced distribution of the CanMEDS roles.

[Pain medicine as a cross-sectional subject in German medical schools. An opportunity for general pain management]. / Das Querschnittsfach "Schmerzmedizin". Chance für die Allgemeine Schmerzmedizin.

BACKGROUND: Unrelieved pain is a substantial public health concern owing in part to deficits in clinical expertise among physicians. In most medical faculties worldwide, teaching on pain and pain management is either nonexistent or limited to a small number of students attending voluntary courses. In light of the fact that pain is the most frequent reason to seek medical advice, the lack of formal training of pain medicine is considered the leading reason for inadequate pain management. Therefore, the patients' unmet needs for adequate diagnosis and therapy call for action. SITUATION: Pain assessment and effective pain management should be a priority in the health care system. The limited number of pain specialists available in hospitals and primary care and CME (continuous medical education) activities focusing on pain are not sufficient to solve the problem. Every practicing physician should, therefore, have basic knowledge of the most prominent painful conditions and management strategies. To achieve this goal, pain medicine should become an integral part of the undergraduate curriculum for medical students. In Germany, pain medicine became a mandatory subject in undergraduate medical studies in 2012. PERSPECTIVE: The introduction of pain medicine into the undergraduate curriculum in Germany is a major challenge regarding the development and implementation processes. This article describes current instruments and implementation strategies for pain medicine as a new cross-sectional subject in Germany.

Ecological divergence and speciation between lemur (Eulemur) sister species in Madagascar.

Understanding ecological niche evolution over evolutionary timescales is crucial to elucidating the biogeographic history of organisms. Here, we used, for the first time, climate-based ecological niche models (ENMs) to test hypotheses about ecological divergence and speciation processes between sister species pairs of lemurs (genus Eulemur) in Madagascar. We produced ENMs for eight species, all of which had significant validation support. Among the four sister species pairs, we found nonequivalent niches between sisters, varying degrees of niche overlap in ecological and geographic space, and support for multiple divergence processes. Specifically, three sister-pair comparisons supported the null model that niches are no more divergent than the available background region. These findings are consistent with an allopatric speciation model, and for two sister pairs (E. collaris-E. cinereiceps and E. rufus-E. rufifrons), a riverine barrier has been previously proposed for driving allopatric speciation. However, for the fourth sister pair E. flavifrons-E. macaco, we found support for significant niche divergence, and consistent with their parapatric distribution on an ecotone and the lack of obvious geographic barriers, these findings most strongly support a parapatric model of speciation. These analyses thus suggest that various speciation processes have led to diversification among closely related Eulemur species.

[Cross-sectional field 14 pain medicine. Implementation of the German Pain Society (DGSS) core curriculum in the model study course MaReCuM]. / Querschnittsbereich 14 Schmerzmedizin. Umsetzung des Kerncurriculums der Deutschen Schmerzgesellschaft im Modellstudiengang MaReCuM.

BACKGROUND: The recent introduction of amendments to the medical licensure laws led to the introduction of the field of pain medicine into the study program "Human Medicine". The implementation has to be completed by all medical faculties before 2016. MATERIAL AND METHODS: Pain medicine was implemented into the model study course"MaReCuM" at the medical faculty in Manheim as a compulsory subject in the year 2010. It is structured into five sections in a longitudinal manner. The core section is the "pain awareness week" in the fifth academic year of the medical studies. The content and structure is based on the German Pain Society (DGSS) curriculum. For the purpose of this study the examination results and the student evaluation forms from the academic years 2010/2011 and 2011/2012 were analyzed. RESULTS: The students regarded pain medicine as being highly relevant concerning its impact on the professional activities. The competence to develop a specific and individual therapy was of special interest. A good coordination of the contents of teaching between preclinical and clinical teaching was considered to be of major importance. CONCLUSIONS: The DGSS curriculum is a useful tool for the implementation of pain medicine in a study program. In order to improve access to basic pain medicine in general, a combined teaching program consisting of pain medicine and general medicine could be helpful. Pain medicine could be used as a guide for teaching contents of outpatient medicine.

Skin innervation at different depths correlates with small fibre function but not with pain in neuropathic pain patients.

BACKGROUND: Neuropathy can lead not only to impaired function but also to sensory sensitization. We aimed to link reduced skin nerve fibre density in different levels to layer-specific functional impairment in neuropathic pain patients and tried to identify pain-specific functional and structural markers. METHODS: In 12 healthy controls and 36 patients with neuropathic pain, we assessed clinical characteristics, thermal thresholds (quantitative sensory testing) and electrically induced pain and axon reflex erythema. At the most painful sites and at intra-individual control sites, skin biopsies were taken and innervation densities in the different skin layers were assessed. Moreover, neuronal calcitonin gene-related peptide staining was quantified. RESULTS: Perception of warm, cold and heat pain and nerve fibre density were reduced in the painful areas compared with the control sites and with healthy controls. Warm and cold detection thresholds correlated best with epidermal innervation density, whereas heat and cold pain thresholds and axon reflex flare correlated best with dermal innervation density. Clinical pain ratings correlated only with epidermal nerve fibre density (r = 0.38, p < 0.05) and better preserved cold detection thresholds (r = 0.39, p < 0.05), but not with other assessed functional and structural parameters. CONCLUSIONS: Thermal thresholds, axon reflex measurements and assessment of skin innervation density are valuable tools to characterize and quantify peripheral neuropathy and link neuronal function to different layers of the skin. The severity of small fibre neuropathy, however, did not correspond to clinical pain intensity and a specific parameter or pattern that would predict pain intensity in peripheral neuropathy could not be identified.

Cross-over evaluation of electrically induced pain and hyperalgesia.

Background Anewexperimental protocol of electrically induced pain and hyperalgesia was established to examine orally administered drugs. In a randomized, double-blind, placebo-controlled cross-over study this experimental protocol was used to assess the effects of paracetamol. Methods Twenty-four subjects were enrolled in this study. The magnitude of pain, axon reflex flare, and areas of pin-prick hyperalgesia and touch-evoked allodynia were assessed in two consecutive sessions; prior to, and 2 h after drug administration. This protocol was repeated after 1 week. Subjects were randomized to receive either paracetamol (2 g) or a placebo. Results In comparison to the placebo arm there were no significant effects of paracetamol on pain, hyperalgesia, allodynia, or axon reflex flare. Pain and flare responses were highly reproducible on the same day (r = 0.77 and r = 0.79, respectively), and after 1 week (r = 0.6 and r = 0.71, respectively). The correlation between areas of hyperalgesia and allodynia was, however, significantly improved when the protocol was repeated on the same day (r = 0.8 and r = 0.75), as opposed to after a week (r = 0.54 and r = 0.53). Discussion The electrical pain model is a well established method for the assessment of intravenously applied analgesics. In order to assess effects of orally applied drugs the model had to be modified: for the assessment of hyperalgesia and allodynia a protocol repeating the model within 1 day proved to have advantages over repetition after 1 week.

Comparison of electrically induced flare response patterns in human and pig skin.

OBJECTIVE: We compared the characteristics of neurogenic flare responses in human and pig skin to establish a translational research animal model. MATERIAL AND SUBJECTS: Eight domestic pigs and six male subjects were investigated. TREATMENT: Electrical pulses were delivered transcutaneously with increasing current intensities, pulse frequencies and pulse widths. METHODS: Inflammatory skin responses were recorded by laser Doppler imaging and analyzed by ANOVA and Fisher's (LSD) post hoc test. RESULTS: Transcutaneous stimuli of 5 mA onward induced a significant flare development in humans. In the pig, significantly lower currents of 2.5 mA already induced a flare response. Smaller flare sizes of about 3.5 cm(2) were analyzed. The flare continuously declined despite ongoing stimulation. CONCLUSIONS: Lower excitation thresholds and smaller receptive fields of nociceptors can be suggested in pigs. Impaired neuropeptide release, altered vesicle replenishment, different neuropeptide sensitivity, or insufficient peripheral decoding of action potentials may contribute to steadily decreasing flare responses. These attributes may be objectives of pre-clinical anti-hyperalgesic studies and their accurate analysis in pigs reveals a particularly sensitive translational animal model for nociceptor researches.

Cross sectional and longitudinal study on selenium, glutathione peroxidase, smoking, and occupational exposure in coal miners.

OBJECTIVES: To understand the variations of selenium (Se) concentration relative to changes in occupational exposure to coal dust, taking into account age and changes in smoking habits in miners surveyed twice, in 1990 and 1994. To better understand the relation of Se concentration with glutathione peroxidase activities (GSH-Px) in these miners. METHODS: In 1994, blood samples were obtained from active (n=131) and retired (n=40) miners without coal worker's pneumoconiosis, in whom Se concentration was available at both surveys and in whom International Labour Organisation (ILO) profusion grade had not been changed. Active miners were exposed to high dust concentrations (n=48) or low dust concentrations (n=83). Miners were classified into three subgroups according to their estimated cumulative exposure to dust, and into three subgroups according to their smoking habits. RESULTS: Selenium concentration and GSH-Px activities were significantly lower in active than in retired miners (Se adjusted means: 62.6 v 72.2 ng/ml p=0.01). Moreover, Se concentration was lower in miners exposed to high compared with those exposed to low dust concentrations (adjusted means: 59.4 v 65.8). In miners exposed to high dust concentrations, Se concentration was significantly lower whereas erythrocyte GSH-Px activity was significantly higher in the subgroup with estimated cumulative exposure >68 mg/m(3).y. In all miners, plasma GSH-Px activity was correlated with Se concentration (r=0.22, p<0.005). The 4 year Se changes were negatively related to exposure to high dust concentrations and positively related to change in exposure from high to retirement and to change from smoker to ex-smoker (p=0.01). CONCLUSION: The variations of Se concentration in relation to changes in occupational exposure to coal dust and in smoking habits, and the close correlation found between plasma Se concentration and GSH-Px activity suggest that both are required in antioxidant defence. These results agree well with the hypothesis that the decrease in Se concentration reflects its use against reactive oxygen species generated by exposure to coal mine dust and by smoking.

Relations between occupational exposure to coal mine dusts, erythrocyte catalase and Cu++/Zn++ superoxide dismutase activities, and the severity of coal workers' pneumoconiosis.

OBJECTIVES: To better understand the relations between occupational exposure, blood antioxidant enzyme activities, total plasma antioxidant concentration, and the severity of coal workers' pneumoconiosis (CWP). METHODS: Blood samples were obtained from miners without CWP exposed to low dust concentrations for > or = 4 years at the time of the study (n = 105), or exposed to high dust concentrations for > or = 14 years at the time of the study (n = 58), and from retired miners with CWP (n = 19). Miners without CWP were classified into three subgroups according to their estimated cumulative exposure to dust. Chest x ray films were obtained for each miner. Miners were classified in five subgroups according to their International Labour Organisation (ILO) profusion grades. Univariate tests were completed by multiple linear regression analyses. RESULTS: The estimated cumulative exposure to dust was strongly positively related to erythrocyte catalase activity and strongly negatively related to Cu++/Zn++ SOD activity only in miners exposed to high dust concentrations for > or = 14 years at the time of the study (F tests p = 0.006 and p = 0.004 respectively). Moreover, catalase activity was strongly related to the severity of CWP expressed as five subgroups of ILO profusion grades (F test p = 0.003); the greatest difference in the mean values was found between the group of 1/1 to 1/2 ILO profusion grades and the group of 2/1 to 3/3 ILO profusion grades. CONCLUSION: These results are in good agreement with the hypothesis that production of reactive oxygen species may be an important event in the exposure to coal mine dusts and the severity of CWP. Erythrocyte catalase and Cu++/Zn++ SOD activities are more closely related to recent exposure to high dust concentrations than to cumulative exposure, and could be considered as biological markers of exposure rather than as markers of early adverse biological effect.

Relationship between blood antioxidants and occupational exposure to polycyclic aromatic hydrocarbons in coke oven workers.

BACKGROUND: We investigated if blood Cu++/Zn++ superoxide dismutase, glutathione peroxidase, and catalase activities are increased and total plasma antioxidant concentration is decreased in coke oven workers exposed to polycyclic aromatic hydrocarbons. METHODS: Ninety-six coke oven workers participated in the study. Nonexposed workers (n = 105) were randomly sampled among power plant workers in the same age range. The examination included a questionnaire on health status, occupational history, smoking, and dietary habits. Blood samples completed the examination. Coke oven workers were classified into low-, middle-, and high-exposure groups based on the benzo[a]pyrene (B[a]P) air concentrations and were further classified into the categories "topside" and "non-topside," according to their proximity to the ovens. RESULTS: Erythrocyte glutathione peroxidase activity increased with age (r = 0.18, P = 0.061) in power plant workers, whereas plasma glutathione peroxidase activity decreased with age (r = -0.18, P = 0.068) and erythrocyte glutathione peroxidase activity was inversely correlated with the number of cigarettes per day (r = -0.28, P = 0.08) in coke oven workers. Comparison of blood antioxidant enzyme activities and total plasma antioxidant concentration between coke oven and power plant workers showed that erythrocyte glutathione peroxidase activity was significantly lower in coke oven workers, even after adjustment for potential confounding factors. No differences were found either in other blood antioxidant enzyme activities or in total plasma antioxidant concentration between coke oven and power plant workers. Moreover, no trends toward decreased glutathione peroxidase activity among the three subgroups of B[a]P exposure were observed, and no differences either in blood antioxidant enzyme activities or in total plasma antioxidant concentration between the two groups of job categories were found. CONCLUSIONS: Production of reactive oxygen species seems not to be increased in coke oven workers.

Erythrocyte antioxidant enzyme activities in coal miners from three French regions.

This study investigated whether differences in the prevalence and severity of coal workers' pneumoconiosis (CWP) between three coal mines could be related to differences in oxidative stress exposure as evaluated in vivo through red-blood-cell antioxidant enzyme activities. Blood samples were obtained from 229 miners selected according to their occupation and their pneumoconiotic status. The following biomarkers were evaluated: erythrocyte catalase, Cu2+/Zn2+ superoxide dismutase (Cu2+/Zn2+ SOD), and glutathione peroxidase activities. Antioxidant enzyme activities did not differ significantly between the group of surface workers in Lorraine and the group of underground miners without CWP in Lorraine and in the other coal mines. Erythrocyte Cu2+/Zn2+ SOD activity was slightly decreased in the group of active underground miners with simple pneumoconiosis as compared with the group of miners without CWP in Nord/Pas-de-Calais. No effect was seen between retired miners at different stages of CWP. Our findings indicate that differences in the prevalence and severity of CWP do not seem to be related to various oxidative activities of coal dust particles, at least as reflected by measurements of antioxidant enzyme activities in circulating erythrocytes in this study.