The subjective perception of professional self was studied for a sample of Medical Laboratory Technologists (MLTs) employed in Clinical Chemistry in Sweden. The sample (N = 488) consisted of a randomized tenth of members of their trade union. A mailed questionnaire with 21 items concerning self-description compared with peers in a seven-point Likert type scale was completed by 332 (68%). There was no significant overall difference concerning the four principal types of workplace: Clinical Chemistry, Blood Serology, Primary Care and Clinical Chemistry/Blood Serology. The main difference was found between those in managerial posts (N = 72) and the other MLTs (N = 260). Factor analysis showed three principal components, labelled Professionalism, Work Ethic, and Empathy, but also a different composition of variables of the components for the manager group compared with the non-manager group.

Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome that arises in liver-impaired subjects. Patients with HE display various neuropsychiatric symptoms including affective disturbances and may therefore likely receive treatment with novel thymoleptics like citalopram (CIT). The simultaneous pharmacokinetic and pharmacodynamic outcome of the commonly used serotonin-selective thymoleptic drugs in liver-impaired subjects with pending chronic HE is far from understood today. We therefore investigated the effects of chronic, body-weight-adjusted (10 mg ╖ kg-1 ╖ day-1), treatment with CIT in rats with and without portacaval shunts (PCS). Open-field activity was monitored. The 5-HT, 5-HIAA, noradrenaline (NA), and dopamine (DA) output were assessed in the frontal neocortex. The racemic levels of CIT and its metabolites DCIT and DDCIT, including the S- and R-enantiomers, were determined in serum, brain parenchyma, and extracellular fluid. The rats with PCS showed higher (2-3-fold) levels of CIT than rats undergoing a sham treatment with CIT in all compartments investigated. The PCS rats also showed elevated levels of DCIT and DDCIT. No major differences in the S/R ratios between PCS rats and control rats could be detected. The CIT treatment resulted in neocortical output differences between PCS rats and control rats mainly within the 5-HT and DA systems but not within the NA system. For the 5-HT system, this change was further evidenced by outspoken elevation in 5-HT output after KCl-depolarizing challenges. Moreover, the CIT treatment to PCS rats was shown to "normalize" the metabolic turnover of 5-HT, measured as a profound lowering of a basal elevation in the 5-HIAA levels. The CIT treatment resulted in an increased or "normalized" behavioral activity in the PCS group. Therefore, a dose-equal chronic treatment with CIT in PCS rats produced pharmacokinetic and pharmacodynamic changes not observed in control rats. The results further support the contention of an altered 5-HT neurotransmission prevailing in the chronic HE condition. However, the tentatively beneficial behavioral response also seen following chronic CIT treatment to PCS rats in this study has to be viewed in relation to both the pharmacokinetic and pharmacodynamic changes observed.

A person's belief is seen as a set of assumptions, depending on perceptions, and formed with the influence of experiences and social culture. With the aim of understanding the beliefs about the genesis of their illness, 118 (59 + 59) women with different stages of breast cancer were interviewed. Half of the sample had chosen complementary care in an anthroposophical hospital, and the other half was a matched group. Qualitative content analysis was used. Three themes emerged: (1) belief in a link to life lived (71%), (2) heredity as the sole genesis (4%), and (3) rejection of the question (25%). Under beliefs in a link to life lived, external aspects to the patient's own life (eg, diet and lifestyle) were cited, as well as inner aspects such as psychosocial problems and stress. The findings show that women are well informed about medical facts, although their beliefs reveal a holistic approach. The women's beliefs, where inner psychosocial factors are uppermost, point to a reverse of the causal ranking of medical advisors. The difference between the groups was that the matching sample was more likely to reject the influence of possible causes from life lived. In a caring perspective, women's perceptions of the genesis of their illness are in some cases turned to creative health activities that may increase well-being. © 2006 Lippincott Williams & Wilkins, Inc.

In this study, qualitative content analysis was used in order to understand the reported changes of life perspective in interviews with 59 women with breast cancer who were admitted to complementary care. The aim of this research was to study women's perceived consequences as well as perceived causes of breast cancer and to explore aspects of importance to the women. The material was collected in semistructured interviews from women with breast cancer at different stages of the disease. The women received complementary care at an anthroposophic clinic in Sweden. Findings showed that these women's view of their relationships with others grew more valuable. Their self-confidence and experience of strength improved, and they regarded life as being more enriched. A change in their disposition towards becoming more fragile and low-spirited was experienced as a hardship by the women. An interesting finding was that the patients described the aetiology of the disease from several interacting perspectives, which also affected their ideas of how to achieve well-being and health. The findings support the view that changes of both benefit and harm are present in the experience of breast cancer.

A previous study indicated that patient narratives include experiences of suffering caused or increased by health-care encounters. The aim of this study was to interpret and understand the meaning of patients' experiences of suffering related to health care from an ethical, existential and ontological standpoint. Sixteen women with breast cancer in Sweden and Finland took part in qualitative interviews analysed with a hermeneutic, interpretive approach. The outcome showed that suffering related to health care is a complex phenomenon and constitutes an ethical challenge to health-care personnel. The women's experiences of suffering related to health care tended to be of similar seriousness as their experiences of suffering in relation to having cancer. In an ethical, existential and ontological sense, suffering related to health care is basically a matter of neglect and uncaring where the patient's existential suffering is not seen and she is not viewed as a whole human being.

1. Several studies suggest an association between venous thromboembolism and the use of antipsychotic drugs, especially clozapine, but the biological mechanisms are unknown. It has been suggested that antipsychotic drugs enhance aggregation of platelets and thereby increase the risk of venous thrombosis. The purpose of the present study was to examine the effects of clozapine and its main metabolite, N-desmethyl clozapine, as well as olanzapine, risperidone and haloperidol, on platelet adhesion and aggregation and on plasma coagulation in vitro. 2. Blood was collected from healthy subjects free of medication. Platelet adhesion to different protein surfaces and aggregation were measured in microplates. The coagulation methods of activated partial thromboplastin time (APTT) and prothrombin time were performed in platelet-poor plasma. 3. Clozapine was the only compound that increased platelet adhesion and aggregation and shortened APTT. The effect appeared at therapeutic concentrations and was significant but weak. 4. This weak effect of clozapine on haemostasis may explain, in part, the association of this compound and venous thromboembolism. © 2007 The Authors.

Background. Nurses' attitudes towards research have been illuminated in many studies. However, there is still a need for more knowledge about the attitudes and awareness of undergraduate nursing students. Aim. To investigate Swedish undergraduate nursing students' attitudes towards and awareness of research and development within nursing, and to illuminate factors that may have an impact on their attitudes and awareness. Methods. A questionnaire consisting of three parts: demographic data, attitude scale, and research awareness was used. Parametric and nonparametric statistics were used. Two hundred and one students participated in the study and the response rate was 77%. Cronbach's alpha test on the seven factors was between 0.52 and 0.80. Results. Most of the students had positive attitudes towards nursing research. More than half (60%) of the students expected to make use of nursing research sometime in the future and about 25% had never read any of the scientific nursing journals. The majority (77%) of the students were acquainted with at least one Swedish researcher, but few had attended a doctoral dissertation. Students with an interest in some particular development or research area in nursing were significantly more positive and expected to make use of nursing research more frequently. Other variables that were found to have some impact upon attitudes were gender, age and additional academic studies. Conclusion. Nursing students had an overall positive attitude towards nursing research and their interest in a particular development or research area was the most important variable for their attitudes and expected use of nursing research in the future. Therefore, it would seem to be important to encourage the students' interest in specific development/research areas of nursing during their education. In spite of the nursing students' positive attitudes to nursing research, the study demonstrates the theory-practice gap is still present to some degree.

Aim of the study. The aim was to develop and test an assessment instrument in order to study attitudes towards research and development within nursing among randomly selected professional nurses, registered nurses (RNs). Background. The investigation was initiated because of the development within nursing and nursing education in Sweden towards better knowledge about research for the last four decades. Methods. A questionnaire was designed, consisting of three parts: (1) demographic data, (2) attitude scale and (3) research awareness. Appropriate psychometric statistics were used such as factor analysis and parametric as well as nonparametric statistics to compare groups. The form was distributed to 407 randomly selected RNs. Results. The response rate was 71% (n = 289). The respondents were from four different examination years, representing four different nursing education systems in Sweden. Factor analysis (Maximum Likelihood and Oblimin rotation) gave seven factors with a total variance of 58% and Cronbach's a between 0╖60 and 0╖84. The factors were labelled 'Research language', 'Need of research knowledge', 'Participation', 'The Profession', 'Meaningfulness', 'Study literature' and 'Developing -Resources'. The results indicated that the respondents in general had positive attitudes towards nursing research. There were significant differences between the examined groups. The group examined in 1966 appeared as the least positive group. Forty-six per cent never or seldom utilized nursing research findings in their daily practice. About half of the respondents never read research reports. Conclusion. The results indicated that the new instrument is sensitive for measuring professional nurses' attitudes towards research and development in nursing. Even if the respondents had a positive attitude towards research and development, there was a poor application in their daily work. Further, the respondent's age, the year of RN examination and acquisition of research skills seemed to be of importance for the attitudes.

Objective: Many patients with cancer, women more often than men, use complementary and alternative medicine (CAM) and care. Our aim was to examine coping over 5 years (November 1995 to January 1999) in two samples of women with breast cancer who were treated with anthroposophic care or conventional medical treatment. The present study is part of a larger study of the outcome of anthroposophic care for women with breast cancer. Design: A nonrandomized controlled trial design was used with individual matching and repeated measurements on six occasions (at admission, 1 month, 3 months, 6 months, 1 year, and 5 years). The matching was based on the following variables: stage of disease at entry, age, treatment during the 3 months before entering the study, and prognosis. Setting: An anthroposophic hospital and conventional hospitals in Sweden. Subjects: Sixty (60) women treated with anthroposophic medicine and 60 women from an oncology outpatient department participated. Forty-nine (49) women in anthroposophic care and 51 in the outpatient group survived 1 year, 26 women in anthroposophic care and 31 in the outpatient group survived 5 years. Intervention: An anthroposophic care program. Outcome measure: Coping was measured using the Mental Adjustment to Cancer scale. Repeat measures of analysis of variance (ANOVA) were used for within-group comparisons, and effect size (ES) was used for between-group comparisons. Results: The women in anthroposophic care showed more passive and anxious coping on admission, but this decreased over time. In the women in anthroposophic care, there were small ES improvements in fighting spirit and passive, anxious coping at 4 of the measured timepoints compared to admission. Conclusion: The choice of anthroposophic care could be seen as a possible way to cope with emotional distress in this group of women with breast cancer. © Mary Ann Liebert, Inc.

The life satisfaction questionnaire (LSQ) was developed for use in conventional and complementary/anthroposophic care to assess the quality of life/life satisfaction of Swedish women with breast cancer. The first attempt to test the reliability and validity was in a sample of women with breast cancer (n = 362), the second in a random sample of Swedish women (n = 257). A theoretical model with six latent and 34 manifest variables was formulated. The aim of the present study was to perform confirmatory factor analyses using structural equation modelling. The software STREAMS was used. An additional sample of men (n = 263) was randomly selected from the Swedish population register. Confirmatory factor analyses were performed for the combined sample of women and men (n = 520) and for the women with breast cancer. The result of the confirmatory factor analyses showed that the factor structure of the original model was confirmed. The factors were called physical symptoms (PS), sickness impact (SI), quality of everyday activities (QDA), socio-economic situation (SES), quality of family relation (QFA), and quality of close friend relationship (QFR).

Aims: In Sweden, suicides by drug poisoning have decreased in the population at large during the past two decades. However, drug poisoning suicides increased among the elderly during this period. Suicides by benzodiazepine poisoning increased in this age group despite a reduction in prescription sales of these drugs. This study aims therefore to determine the role of benzodiazepines in suicide late in life. Methods: Information concerning all definite suicides and deaths due to "undetermined" causes recorded among Swedish citizens aged 65 and above during 1992-96 was obtained from the Cause-of-Death Register. Death certificates were scrutinized to determine the type of drug employed in drug-related suicides. Results of the post mortem screening for drugs and alcohol were then examined. Results: A benzodiazepine was implicated in 216/548 (39%) of the drug poisoning suicides recorded among the elderly. Death certificates revealed that a benzodiazepine was the sole agent in 72% of these cases. Flunitrazepam or nitrazepam were implicated in 90% of the single benzodiazepine suicides. In addition to the suicides classified as drug poisonings, 82 cases were found in which a drug may have contributed to the cause of death. Benzodiazepines predominated. The terminal cause of death was drowning, often in the victim's own bathtub, in three-quarters of these cases. The annual fatality ratios for the newer benzodiazepine-like hypnotics zopiclone and zolpidem appear to be on the rise. Conclusion: Benzodiazepines, especially the hypnotics flunitrazepam and nitrazepam, are common in drug poisoning suicides in the elderly and should be prescribed with caution for this age group.

In this study, patient records from 80 male patients, aged 43-76, undergoing first-time coronary artery bypass surgery were evaluated with regard to nurses' documentation on sleep during the first four postoperative days. This documentation was classified into descriptions of quality and quantity of sleep. Notations on sleep were found in 69-86% of patient records each night, and was most common the second night. Descriptions of both quality and quantity of sleep occurred in only 12 out of 320 patient-nights. Notes regarding duration of sleep were found for 146 patient-nights (45.6%), of which 103 (32.2%) contained sleep disturbances. Information on quality of sleep was given for 116 patient-nights (36.3%), with only 38 patient-nights (11.9%) of sleep disturbances. For 72 patient-nights, documentation of the patients' sleep was lacking. Frequent awakening was the most common sleep disturbances noted during all but the first night, when continuous awakening dominated. We conclude that the nurses' documentation regarding sleep and sleep disturbances varied over a wide range, with a mixture of quantitative and qualitative information, and that more structured descriptions are needed.

The aim of this study was to: (i) test different instruments that focused on sleep, quality of life and personal adjustment in order to evaluate the usefulness of these instruments in a larger study; and (ii) to describe self perceptions of sleep and life situation by patients who had undergone coronary artery bypass grafting (CABG). A one-group pre-test repeated post-test design was used. Six men aged between 51 and 70 years were interviewed, and 24 h polysomnographic recordings were performed before and after the operation. The interviews indicated disturbed sleep and changes in behaviour and mental state immediately postoperatively. Postoperatively the polysomnographic recordings revealed a significant decrease in mean duration of sleep, mean percentage of stage 3-4 sleep and mean rapid eye movement (REM) sleep. One month after surgery the quality of life was improved, while moderate anxiety and sensation of incisional pain persisted. The measurements used in this pilot study provide valuable information into the understanding of altered sleep, quality of life and personal adjustment following CABG.

Methylmercaptopurine riboside (meMPR), a cellular metabolite of 6-mercaptopurine (6-MP), is a potent inhibitor of de novo purine synthesis (DNPS). Human MOLT4 T-lymphoblastic leukaemia cells that have acquired resistance to 6-MP or 6-thioguanine (6-TG) as a consequence of defective transport exhibit enhanced sensitivity to meMPR. HPLC-based analysis of the transport of meMPR revealed normal uptake of this compound by our thiopurine-resistant cell sublines, suggesting a route of transport distinct from that for 6-MP and 6-TG. Studies on the wild-type parental leukemic cells showed that adenosine, dipyridamole and nitrobenzylthioinosine inhibit uptake of meMPR to a significant extent, whereas Na+ ions have no influence on this process. Transfection of these leukemic cells with small interference RNA molecules targeting the gene encoding the first member of the family of equiliberative nucleoside transporters (ENT1) strongly reduced the initial rate of meMPR transport. Our resistant cell lines exhibited 30-52% reductions (p < 0.005) in their levels of mRNA encoding several proteins involved in de novo purine synthesis, i.e., aminoimidazole carboxamide ribonucleotide formyltransferase, glycinamide ribonucleotide transformylase and guanine monophosphate synthetase. Consequently, the rate of de novo purine synthesis in these resistant sublines was decreased by 50%. Furthermore, the levels of ribonucleoside triphosphates in these cells were significantly lower than in the non-resistant parental cells. In combination, a reduced rate of de novo purine synthesis together with low levels of ribonucleoside triphosphates can explain the enhanced sensitivity of our thiopurine-resistant cell lines to meMPR. In this manner, meMPR bypasses the mechanisms of resistance to thiopurines and is even more cytotoxic towards resistant than towards wild-type cells. © 2006.

In order to better understand the mechanisms of resistance to thiopurines, we studied two sublines of the MOLT4 T-lymphoblastic leukemia cell line, resistant to 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We found that the underlying mechanism of resistance in both resistant cell lines was a markedly reduction in initial transport of 6-MP (3- and 5-fold, respectively, in 6-MP- and 6-TG-resistant cells). No significant alteration of activities of hypoxanthine-guanine phosphoribosyl transferase, thiopurine methyltransferase or inosine monophosphate dehydrogenase, the key enzymes involved in the metabolism of thiopurines was detected. We conclude that defected initial transport of thiopurines by cells may very well explain their resistance to these drugs. Copyright © Taylor & Francis Group, LLC.

Mechanisms of resistance to thiopurines, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) were investigated in human leukemia cell lines. We developed two 6-MP- and 6-TG-resistant cell lines from the human T-lymphoblastic cell line (MOLT-4) by prolonged exposure to these drugs. The resistant cells were highly cross resistant to 6-MP and 6-TG, and exhibited marked reduction in cellular uptake of 6-MP (70% and 80%, respectively). No significant modification of the activities of hypoxanthine-guanine phosphoribosyl transferase, thiopurine methyltransferase or inosine monophosphate dehydrogenase was observed. Real-time PCR of concentrative nucleoside transporter 3 (CNT3) and equilibrative nucleoside transporter 2 (ENT2) of resistant cells showed substantial reductions in expression of messenger RNAs. Small interfering RNA designed to silence the CNT3 and ENT2 genes down-regulated the expression of these genes in leukemia cells. These decreases were accompanied by reduction of transport of 6-MP (47% and 21%, respectively) as well as its cytocidal effect (30% and 21%, respectively). Taken together these results show that CNT3 and ENT2 play a key role in the transport of 6-MP and 6-TG by leukemia cells. From a clinical point of view determination of CNT3 and ENT2 levels in leukemia cells may be useful in predicting the efficacy of thiopurine treatment. © 2006 Elsevier Inc. All rights reserved.

The accuracy of two clinical assays, the enzyme-multiplied immunoassay (EMIT) and fluorescence polarization immunoassay (FPIA2), universally employed for measurement of plasma levels of methotrexate (MTX) in children administered a high dose of this drug for treatment of acute lymphoblastic leukemia was evaluated here. Because of its superior specificity, sensitivity, and precision, high performance liquid chromatography (HPLC) was selected as the reference method with which the other two procedures were compared using approximately 420 different plasma samples for method comparison. 7-Hydroxymethotrexate (7-OHMTX), the major plasma metabolite of MTX, that can be detected in plasma at relatively high concentrations for long periods following infusion of a high dose of MTX, was also quantitated by HPLC. Forty-two and 66 h after infusion, the plasma level of MTX was overestimated in 2% and 3% of the samples by the FPIA2 procedure in 5% and 31% by the EMIT assay. The overall correlation coefficients (r2) for the values obtained by FPIA2 or EMIT versus those based on HPLC were 0.989 and 0.663, respectively. The presence of 7-OHMTX exerted a highly significant influence (p = 0.0007 as determined by the unpaired t-test) on MTX measurement by the EMIT assay. We conclude that the rapid automated procedures routinely used at present and in particular EMIT, suffer from cross-reactivity with metabolites of MTX. Thus, the relatively high percentage of samples in which the level of MTX is overestimated at check-points by EMIT may result in longer periods of hospitalization, higher costs and prolonged administration of elevated doses of "rescue" leucovorin with an increased risk for relapse. © 2004 Elsevier B.V. All rights reserved.

Aims: To detect risk factors for sudden death from heroin injection. Design: Evaluation of data from forensic investigations of all fatal cases of suspected heroin death in a metropolitan area. Only cases with detectable morphine and 6-monoacetylmorphine (6-MAM) in blood were included in order to select heroin intoxication cases. Setting: Stockholm, Sweden. Measurements: Autopsy investigation and toxicological analysis of blood and urine: and police reports. Findings: In two-thirds of the 192 cases, death occurred in public places, and mostly without any time delay. Blood concentrations of morphine ranged from 50 to 1200 ng/g, and of 6-MAM from 1 to 80 ng/g. Codeine was detected in 96% of the subjects. In the majority of cases the forensic investigation indicated polydrug use, the most common additional findings being alcohol and benzodiazepines. However, in one-quarter of the cases other drug combinations were found. Previous abstinence from heroin and use of alcohol were identified as risk factors. For 6-MAM there was also a correlation with the presence of THC and benzodiazepines. Despite a high frequency of heart abnormalities (e.g. myocarditis and focal myocardial fibrosis), these conditions did not correlate with morphine or 6-MAM blood concentrations. Conclusions: We confirm that alcohol intake and loss of tolerance are risk factors for death from heroin use, whereas no connection to heart pathology was observed. Further, prospective, studies should focus on other possible risk factors.

Deoxynucleoside analogues (dNAs) are cytotoxic towards both replicating and indolent malignancies. The impact of fluctuations in the metabolism of dNAs in relation to cell cycle could have strong implications regarding the activity of dNAs. Deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) are important enzymes for phosphorylation/activation of dNAs. These drugs can be dephosphorylated/deactivated by 5′-nucleotidases (5′-NTs) and elevated activities of 5′-NTs and decreased dCK and/or dGK activities represent resistance mechanisms towards dNAs. The activities of dCK, dGK, and three 5′-NTs were investigated in four human leukemic cell lines in relationship to cell cycle progression and cytotoxicity of dNAs. Synchronization of cell cultures to arrest in G0/G1 by serum-deprivation was performed followed by serum-supplementation for cell cycle progression. The activities of dCK and dGK increased up to 3-fold in CEM, HL60, and MOLT-4 cells as they started to proliferate, while the activity of cytosolic nucleotidase I was reduced in proliferating cells. CEM, HL60, and MOLT-4 cells were also more sensitive to cladribine, cytarabine, 9-β-d-arabinofuranosylguanine and clofarabine than K562 cells which demonstrated lower levels and less alteration of these enzymes and were least susceptible to the cytotoxic effects of most dNAs. The results suggest that, in the cell lines studied, the proliferation process is associated with a general shift in the direction of activation of dNAs by inducing activities of dCK/dGK and reducing the activity of cN-I which is favourable for the cytotoxic effects of cladribine, cytarabine and, 9-β-d-arabinofuranosylguanine. These results emphasize the importance of cellular proliferation and dNA metabolism by both phosphorylation and dephosphorylation for susceptibility to dNAs. It underscores the need to understand the mechanisms of action and resistance to dNAs in order to increase efficacy of dNAs treatment by new rational. © 2007 Elsevier Inc. All rights reserved.

Activation of nucleoside analogues is dependent on kinases and 5′-nucleotidases and the balance between the activity of these enzymes. The purpose of this study was to analyze deoxycytidine kinase, deoxyguanosine kinase, and 4 different 5′-nucleotidases during cell cycle progression in MOLT-4 cells. The activity of both kinases was cell cycle dependent and increased during proliferation while the activity of cytosolic 5′-nucleotidase I decreased. We could show that the kinase activity was higher than the total nucleotidase activity, which was unchanged or decreased during cell cycle progression. These data may be important in designing modern combination therapy with nucleoside analogues. Copyright © Taylor & Francis Group, LLC.