Single-walled carbon nanotube-induced mitotic disruption.

Carbon nanotubes were among the earliest products of nanotechnology and have many potential applications in medicine, electronics, and manufacturing. The low density, small size, and biological persistence of carbon nanotubes create challenges for exposure control and monitoring and make respiratory exposures to workers likely. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 24, 48 and 96 µg/cm(2) single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 24-72 h at doses equivalent to 20 weeks of exposure at the Permissible Exposure Limit for particulates not otherwise regulated. We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. The data further demonstrated multipolar mitotic spindles comprised 95% of the disrupted mitoses. The increased multipolar mitotic spindles were associated with an increased number of cells in the G2 phase of mitosis, indicating a mitotic checkpoint response. Nanotubes were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 µg/cm(2) SWCNT. Three-dimensional reconstructions showed carbon nanotubes within the centrosome structure. The lower doses did not cause cytotoxicity or reduction in colony formation after 24h; however, after three days, significant cytotoxicity was observed in the SWCNT-exposed cells. Colony formation assays showed an increased proliferation seven days after exposure. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. The increased proliferation that was observed in carbon nanotube-exposed cells indicates a greater potential to pass the genetic damage to daughter cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is an early event in the progression of many cancers, suggesting that it may play a role in both tumorigenesis and tumor progression. These results suggest caution should be used in the handling and processing of carbon nanotubes.

Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos?

The production of carbon nanofibers and nanotubes (CNF/CNT) and their composite products is increasing globally. CNF are generating great interest in industrial sectors such as energy production and electronics, where alternative materials may have limited performance or are produced at a much higher cost. However, despite the increasing industrial use of carbon nanofibers, information on their potential adverse health effects is limited. In the current study, we examine the cytotoxic and genotoxic potential of carbon-based nanofibers (Pyrograf®-III) and compare this material with the effects of asbestos fibers (crocidolite) or single-walled carbon nanotubes (SWCNT). The genotoxic effects in the lung fibroblast (V79) cell line were examined using two complementary assays: the comet assay and micronucleus (MN) test. In addition, we utilized fluorescence in situ hybridization to detect the chromatin pan-centromeric signals within the MN indicating their origin by aneugenic (chromosomal malsegregation) or clastogenic (chromosome breakage) mechanisms. Cytotoxicity tests revealed a concentration- and time-dependent loss of V79 cell viability after exposure to all tested materials in the following sequence: asbestos>CNF>SWCNT. Additionally, cellular uptake and generation of oxygen radicals was seen in the murine RAW264.7 macrophages following exposure to CNF or asbestos but not after administration of SWCNT. DNA damage and MN induction were found after exposure to all tested materials with the strongest effect seen for CNF. Finally, we demonstrated that CNF induced predominantly centromere-positive MN in primary human small airway epithelial cells (SAEC) indicating aneugenic events. Further investigations are warranted to elucidate the possible mechanisms involved in CNF-induced genotoxicity.

Characterizing voltage contrast in photoelectron emission microscopy.

A non-destructive technique for obtaining voltage contrast information with photoelectron emission microscopy is described. Samples consisting of electrically isolated metal lines were used to quantify voltage contrast in photoelectron emission microscopy. The voltage contrast behaviour is characterized by comparing measured voltage contrast with calculated voltage contrast from two electrostatic models. Measured voltage contrast was found to agree closely with the calculated voltage contrast, demonstrating that voltage contrast in photoelectron emission microscopy can be used to probe local voltage information in microelectronic devices in a non-intrusive fashion.

[Psychosocial workload, sick leave, and health-related well being: an empirical study from the perspective of gender research]. / Psychosoziale Arbeitbelastungen, Arbeitsunfähigkeit und gesundheitsbezogenes Wohlbefinden: Eine empirische Studie aus der Perspektive der Geschlechterforschung.

PURPOSE: The aim of this study was to test hypotheses on the consequences of gender role expectations with regard to the extent of work stress, selected health-related measures and their associations. METHOD: Data on psychosocial workload (questionnaire of effort-reward imbalance), sick leave (self-reports of the duration of medically certified sick leave during the past two years) and health-related well being were collected in a representative sample of German full-time employees (n = 666). Hypotheses were tested using analyses of variance (ANOVA) and covariance (ANCOVA) and moderated linear regression analyses. RESULTS: Women reported lower health-related well-being as compared to men while effort-reward imbalance and sick leave did not differ between the sexes. Parents reported slightly longer durations of sick leave during the past two years than childless participants (not significant). The results of stratified linear regression analyses show stronger associations between effort-reward imbalance and both health-related measures for women with children than for men with children, while single men and women do not differ in this regard. CONCLUSIONS: Evidence of this kind can be useful for the purposeful planning and implementation of health promotion measures at work. Women with children would be a group deserving special attention. The findings also point to continuing differences in gender role expectations in the family context.

Short-term outpatient EEG video with induction in the diagnosis of psychogenic seizures.

To analyze the yield of short-term outpatient EEG video monitoring, the authors reviewed data on all patients who underwent this procedure at their center. All patients were suspected of having psychogenic nonepileptic seizures (PNES) on clinical grounds. The total number of cases of short-term outpatient EEG video monitoring was 74. In 49 (66%) cases, the suspected diagnosis of PNES could be confirmed, thereby obviating the need for prolonged inpatient EEG video monitoring.

[A theory-based study on psychosocial workload as an instrument of health promotion in a hospital]. / Theoriegeleitete Mitarbeiterbefragung im Krankenhaus als Instrument betrieblicher Gesundheitsförderung.

Starting with theory-based assessment of workload as experienced by employees of a hospital we aim at facilitating measures of health promotion. Using the effort-reward-imbalance model of psychosocial stress we look for differences in stress experience as related to objective work stressors and for associations of stress experience and subjective health. Two assessments (in 2000 and in 2002) showed pronounced differences in stress experience between professional groups and between points in time, which were both related to differences in objective workload. The expected associations between psychosocial stress and subjective health (assessed only in 2002) could be demonstrated consistently. As was shown by logistic regression analysis the risk for reduced subjective health was roughly 4 times higher for those in the upper tertile of the effort-reward-imbalance index as compared to all others when controlling for age, sex and professional group. Sources of psychosocial workload could be identified which are modifiable by measures of health promotion.

Application of polymerase chain reaction to detect rearrangement of immunoglobulin heavy chain genes in lymphoproliferative disease.

As part of our routine work-up in the diagnosis of lymphoproliferative disease, we used a rapid polymerase chain reaction (PCR) assay to amplify the DNA fragments of the framework 3 (FR3) region of the immunoglobulin heavy (IgH) chain genes. The assay does not involve hybridization, nested priming, or sequencing of the amplified PCR product. It was performed on 66 specimens of B-cell lymphoproliferative disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, hairy cell leukemia and follicular lymphoma. Twenty-six specimens of negative controls, including acute myeloid leukemia, chronic myeloid leukemia in myeloid transformation and idiopathic thrombocytopenic purpura, were also analyzed. The assay was performed with 77% sensitivity and 100% specificity. The standard IgH chain gene rearrangement by Southern blot analysis is reserved for the remaining negative cases if clinically indicated.

Detection of BCL-2 gene rearrangement in follicular lymphoma by polymerase chain reaction and chemiluminescence technique.

The incidence of follicular lymphoma in Saudi Arabia is very low compared to that in Western countries. We analyzed 22 diagnosed cases, based on conventional morphology examination and immunohistochemistry, to detect the Bcl-2 gene rearrangement by polymerase chain reaction (PCR). The DNA was extracted from formalin-fixed paraffin-embedded lymph node tissues by the standard xylene treatment and proteinase K digestion method. Rearrangement of the major breakpoint region was evident in 8 of the 22 cases (36%), determined by visualization of a discrete band hybridized with a chemiluminescence-labeled specific probe. Although the number of cases is small, we believe it denotes a normal detection rate for PCR analysis, using DNA isolated from fixed tissue. With the exception of follicular lymphoma, non-Hodgkin's lymphoma (NHL) analyzed included diffuse large cell lymphoma, lymphoblastic lymphoma, chronic lymphocytic leukemia, mucosa-associated lymphoid tissue and mantle zone lymphomas. No Bcl-2 gene rearrangement was detected in any of these cases. No evidence of Bcl-2 minor cluster sequence gene rearrangement was detected in any of the 38 NHL cases analyzed.

[Employment after the first myocardial infarct and rehabilitation]. / Erwerbstätigkeit nach erstem Herzinfarkt und Rehabilitation.

Which are the determinants of return to work in middle aged myocardial infarction patients? This question was analysed by means of a follow-up study on men between 1986 and 1992 (group 1: n = 64, age = 46.6 (+/- 5.4), 5-6 years follow-up; group 2: n = 36, age = 51.2 (+/- 7.5), 2 years follow up), all of whom underwent a cardiac rehabilitation program in our hospital. Our aim was to determine the predictive power of social and psychological as compared to cardiologic factors. These factors were operating under two relevant conditions: 1. relative social homogeneity of the samples; 2. rehabilitation including qualified cardiologic diagnostic and an interdisciplinary therapeutic program. As a result we found age--at the same time a biologic and a social variable--to be the best independent predictor in logistic regression as in discriminant analysis. Age was followed by hopelessness in the year before MI, ST segment depression in physical stress test and, with restriction, marital status. Thus our study points to three factors limiting employment status: age as a biological and social limit for achievement, ST segment depression as a coronary and ongoing hopelessness as a psychological limit, with a social background of living alone in some cases. It is important for cardiac rehabilitation to take into account not only biological but also social and psychological limits of work capacity. Comprehensive care tries to modify these limits but cannot remove them.

Neutrophil-rich Ki-1-positive anaplastic large cell lymphoma presenting as a testicular mass.

Ki-1-positive large cell lymphoma is an uncommon subtype of lymphoma that may involve lymph nodes as well as a variety of extranodal locations. To the best of our knowledge, the occurrence of such a tumor in the testis has not been previously documented. We report a case of Ki-1-positive large cell anaplastic lymphoma presenting as a testicular mass in a 56-year old Saudi. Immunohistochemical staining revealed positive staining for Ki-1 and UCHL-1, which indicated a T-cell phenotype. This was further confirmed by polymerase chain reaction analysis, which demonstrated a monoclonal cell population with rearrangement of gamma T-cell receptor. Another interesting morphologic feature was the presence of large numbers of neutrophils throughout the tumor. Similar neutrophil-rich lymphomas have been described recently as a special subtype of Ki-1-positive anaplastic large cell lymphoma.

Bajo peso al nacer y morbimortalidad perinatal: hospital General de Medellin julio a septiembre 1987 / Low birth weight and perinatal morbimortality: hospital General de Medellin july september 1987

Estudio prospectivo realizado en el Hospital General de Medellin Colombia, con 1.300 recien nacidos consecutivamente, por medio de un protocolo que contenia los datos de la Historia Clinica materna y perinatal. Se encontro que 10.46% de estos recien nacidos, fueron de bajo peso, y que entre los factores de riesgo materno que fueron mas significativos para el BPN estan la patologia materna durante el embarazo, con el mayor porcentaje para la ruptura prematura de membranas 22.58%. La prematurez fue el factor de riesgo mas significativo entre los fetales, con 50.7% de R.N. pretermino con BPN. La mortalidad perinatal de los R.N. con BPN estudiados, donde fue de solo 1.61%. Podemos concluir que los factores mencionados juegan un papel fundamental en el resultado final madre-recien nacido, y que la incidencia de BPN y la morbimortalidad perinatal no ha variado en los ultimos anos en Latinoamerica

[Significance of the social anamnesis in the rehabilitation of coronary patients]. / Zur Bedeutung der Sozialanamnese bei der Rehabilitation von Koronarkranken.

We studied some indicators of the course of the disease in male patients (N = 45; x age = 46 +/- 5.6 years) who after first myocardial infarction (MI) spent 4-6 weeks in a rehabilitation clinic. The investigation is done to test the following hypotheses: 1. Social distress during the preinfarction phase is related to coping with the disease (namely anxiety) and to some risk factors (overweight, low-density-Lipoprotein). 2. Participation in a stress-management training that aims at enhancement of coping with social distress has positive effects on the course of the disease. This is particularly true in those who are under strong social pressure. Two panel waves, at the beginning and at the end of stationary rehabilitation, where we gathered data on social and standard risk factors, confirmed our hypotheses in part. Anxiety after MI was related to social distress before MI. For both, anxiety and low-density-lipoprotein, we found a significant interaction effect of social distress and stress-management training as a result of a multivariate analysis of variance (MANOVA; SPSS). Given the small sample size the results should be taken as preliminary and should not be overinterpreted.

Sociological concepts in the etiology of chronic disease: the case of ischemic heart disease.

This paper first gives a selective and critical review of conventional sociological variables included into epidemiologic and clinical studies of ischemic heart disease (IHD). In a second section, links between social and biological processes are discussed, and a conceptual sociological approach is developed which relates critical experiences of active distress to impaired long-term control of social status. This approach is elaborated to some extent in order to illustrate possible avenues of future research which strengthen cross-fertilization between medical and social sciences.