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Background: Several rating scales assessing stress-related symptoms of exhaustion have emerged in recent years. However, more knowledge is needed about the performance of these rating scales in patients with stress-related disorders as well as in other patient groups. With the recently developed Karolinska Exhaustion Disorder Scale (KEDS), we compared symptoms of exhaustion in different patient groups that were sorted according to diagnosis. Methods: Patients were sampled consecutively from departments of occupational medicine (DOM) at three Danish hospitals. The total study group comprised 698 care-seeking patients (487 women). Patients with stress-related diagnoses (n = 217; the International Classification of Diseases [ICD]-10 code F43: reaction to severe stress and adjustment disorder) were compared to a diverse group of patients with a range of somatic diagnoses (n = 338) and to patients with other psychiatric diagnoses (n = 143), including subgroups with major depression disorder (n = 34; F32 and F33) and problems related to employment and unemployment (n = 99; Z56). The data were analysed using linear mixed models with the SPSS statistical program. Results: The mean KEDS sum score in patients with stress-related diagnoses (29.3; SD = 8.0) was significantly higher than in patients with other psychiatric diagnoses (25.9; SD = 9.5) and in patients with somatic diagnoses (17.6; SD = 10.8). The subgroup with a major depression disorder had high mean KEDS sum scores (31.4, SD = 8.1), similar to patients with stress-related diagnoses, while the mean KEDS sum score in patients with problems related to employment and unemployment (Z56) was 23.5 (SD = 9.0). Young and old patients scored similarly on KEDS, but in patients with somatic diagnoses, female patients scored significantly higher than male patients. Conclusion: The symptoms of exhaustion measured with KEDS were higher in patients with stress-related diagnoses and major depression disorder than in patients with somatic diagnoses. The intermediate level of the symptoms of exhaustion that were associated with problems related to employment and unemployment, (Z56) compared to the lower level of the symptoms with somatic diagnoses, suggests that KEDS might be useful in detecting mild, prodromal states of exhaustion. This needs further investigation.

Background No previous studies have examined if genetic factors interacts in the relationship between occupational risk factors and hip and knee osteoarthritis (OA). Objective To examine occupational risk factors for Hip and Knee OA leading to Total Joint Arthroplasty, and if gene-exposure interaction, affect the risk factor-outcome relationship. Material and methods In October 2012 all twin pairs alive in the Danish Twin Register (DTR) with at least one in the pair registered in the Danish Hip or the Danish Knee Arthroplasty Registers (DHA/DKA) with a diagnosis of primary OA were sent a detailed questionnaire regarding previous occupation, related exposures and complementary environmental factors. The analyses included cumulated exposures, McNemar`s X 2 tests, and conditional logistic regression including gene-exposure-interaction variables. Results 1181 twins responded (rate 58.9%). Responder analyses did not display any significant difference with non-responders with respect to diagnosis, zygosity and sex. We found a gene-exposure effect modification in hip OA-lifting and lifting-walking with OR`s 17.7 (1.1–280.2) and 10.4 (1.00–107.1), respectively, and a clear dose-response relationship between hip OA and prolonged standing-walking. Significant occupational risk factor in knee OA was kneeling, but no gene-kneeling interaction was detectable. Conclusion Gene-exposure effect modification may be important in the development of hip OA in particular exposures to lifting and lifting-walking, but not in knee OA.

Background Allergic reactions to the common house plant Hoya compacta (HC) have not previously been described. Aims To confirm HC as the cause of rhinoconjunctivitis in three horticultural workers. Methods Greenhouse working conditions were reproduced in our challenge chamber. Results All three cases developed rhinoconjunctivitis when working with HC plants. A control challenge was performed in two cases with iceberg lettuce causing no symptoms. Nasal volume measured by acoustic rhinometry (AR) fell after all three active challenges, but also after one of the control challenges. Conclusions Our study confirms that HC may cause occupational rhinoconjunctivitis and asthma through a Type I hypersensitivity reaction. Specific inhalation challenges, nasal nitric oxide measurement and AR may be useful additional tools in supporting such diagnoses for occupational physicians to consider.

Background: Symptomatic knee osteoarthritis is a highly age and sex associated complex disease. Little is known about the causes behind this age and sex associated increase, or if genetic and environmental factors impacts differently by gender. Our study examined the risk and heritability of primary knee osteoarthritis leading to total knee arthroplasty and whether these differences were attributable to sex and age differences in heritability. Methods: All twins of known zygosity from The Danish Twin Register alive in 1997 were examined in a nationwide population based follow-up study collecting information on all twins recorded in The Danish Knee Arthroplasty from 1997 to follow-up in 2010. Our main outcomes were the cumulative incidence, probandwise concordance rates, heritability, within pair correlations in monozygotic and dizygotic twin pairs and the genetic and environmental influence estimated in models taking into account that individuals may not have had a total knee arthroplasty at follow up. Results: 92,748 twins were eligible for analyses and 576 twins had a record of primary knee osteoarthritis in The Danish Knee Arthroplasty Register at follow-up comprising 358 female and 218 male twin cases. The risk increased particular after the age of 50years displaying significant sex differences in the elderly. In the sex stratified analyses a discrete genetic component was found in females, but in males no genetic component could be detected. In both genders common and unique environmental factors were highly significant. In the sex-adjusted analysis an additive genetic component of 18% (0; 62), a shared environmental component of 61% (25; 97) and an individual environmental component of 21% (6; 36) accounted for the variation in liability to primary total knee arthroplasty. Conclusion: The risk of primary total knee arthroplasty increases significantly after the age of 50years, in particular in females, displaying significant sex differences in the elderly. After sex-adjustment 82% of the variation in liability to primary total knee arthroplasty was attributable to common and unique environmental factors; the remaining 18% of this variation was attributable to additive genetic factors indicating a pivotal impact of environmental factors on this disease.

Chromosome analysis with fluorescent and Giemsa staining revealed trisomy G-21 in almost 100 % of the bone marrow cells in a case of adult acute myelomonocytic leukaemia with equal proportions of granulocytic and monocytic cells. The results indicate a common precursor cell for the two cell series.

A defective uptake of oxygen by peripheral blood granulocytes during phagocytosis, indicating a subnormal phagocytic capacity, has been found in a patient with regional enteritis complicated by pyoderma gangrenosum (PG). During administration of clofazimine and granulocyte function normalized and the skin lesions healed. It is possible that a defective granulocyte function may sometimes be involved in the pathogenesis of PG and that a clofazimine-induced improvement in the function will favour healing of the lesions. The result of treatment in our patient and in other cases recently published indicates that the drug may be worth trying in PG.

Five out of 74 patients with adult coeliac disease (ACD) diagnosed from 1965 through 1977 developed intestinal lymphoma. The age at diagnosis of ACD was 54-63 years (mean 58) and in all patients an initial improvement was noted on a gluten-free diet. The interval between the diagnoses of ACD and lymphoma was 0.5-6 years (mean 3). In 4 patients the diagnosis of lymphoma was preceded by relapse of diarrhoea and loss of weight despite an adequate diet; 2 patients developed perforation of the bowel. In all patients who subsequently developed lymphoma a pronounced lymphocytopenia, 0.4-1.3 X 10(9)/l, was found at the diagnosis of ACD. It is suggested that ACD patients over 40 who have relapse of malabsorption symptoms despite an adequate diet should be investigated for the presence of an intestinal lymphoma. The suspicion of a malignant transformation may be especially strong if a previous, pronounced lymphocytopenia has been recorded. Three patients died 1-12 months after the diagnosis of lymphoma. However, 2 patients are in good condition 14 and 20 months, respectively, after laparotomy and removal of the tumour, indicating that an early diagnosis and treatment may have a reasonably palliative effect in some cases.

In 18 untreated adult patients (median age 62.5 yr) with advanced non‐Hodgkin's lymphoma of unfavourable histology, thymidine labelling indices (LIs) of the lymphoma cells were assessed. The patients were treated with combination chemotherapy and have been followed for 29–60 (median 52) months or until death. The survival curve had a steep fall during the first 2 yr. Between 2–5 yr after treatment there was a flattening of the curve and survival seemed to be similar to the survival expected for a Swedish population matched for age and sex. 11 patients died with 2 yr and 7 patients have survived for a longer period. Age, histopathologic classification and clinical stages were comparable in short‐term and long‐term survivors and treatment was not more aggressive for the long‐term survivors. The LIs were significantly higher (median 8.2) in short‐term survivors than in the long‐term survivors (median 1.4). Long‐term survival following combination chemotherapy of advanced NHL of unfavourable histology seems to be achieved mainly in patients with a low proliferative activity of the lymphoma cells. It is suggested that in NHL a high proliferative activity may facilitate the generation of new mutants and that some of these are spontaneously resistant to various chemotherapeutic drugs. (Less)

Purpose: A prospective comparison of three imaging techniques: thoracic CT, positron emission tomography (PET), and endoscopic ultrasonography (EUS) with fine needle aspiration (FNA), each performed under routine conditions, for the detection of metastatic lymph nodes metastases in patients with lung cancer considered for operative resection. Patients and methods: Following bronchoscopic evaluation, CT, PET, and EUS were performed to evaluate potential mediastinal involvement in 33 consecutive patients with bronchoscopic biopsy/cytology proven (n = 25) or radiologically suspected (n = 8) lung cancer prior to surgery. Surgical histology was used as “gold standard” to confirm the diagnosis of the primary tumor and the mediastinal status in all patients. Histology proved non-small cell lung cancer in 30 patients, neuroendocrine tumor in 1 patient, and benign disease in 2 patients. Results: The mean age of the study group was 61.5 years (range, 41 to 80 years; 23 male patients). CT, PET, and EUS detected mediastinal lymph nodes (size, 0.4 to 1.6 cm) in 15, 14, and 27 patients (21 of which were suspected to be malignant on EUS), respectively. With respect to the correct prediction of mediastinal lymph node stage, the sensitivities of CT, PET, and EUS were 57%, 73%, and 94%. Specificities were 74%, 83%, and 71%. Accuracies were 67%, 79%, and 82%. Results of PET could be improved when combined with CT (sensitivity, 81%; specificity, 94%; accuracy, 88%). The specificity of EUS (71%) was improved to 100% by FNA cytology (EUS-guided FNA), which gave a tissue diagnosis including tumor type, without complications. Conclusions: No single imaging method alone was conclusive in evaluating potential mediastinal involvement in apparently operable lung cancer and routine clinical conditions. A tissue diagnosis is extremely helpful. Because FNA can be performed at the same time as EUS, this combination emerged as the most useful technique in the evaluation of even very small mediastinal metastases of lung cancer. CT seems necessary additionally to evaluate the pretracheal region as well as the rest of the thorax, and PET may be valuable to detect distant metastases.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for B-cell chronic lymphocytic leukaemia (B-CLL) is based on data from 20 randomised controlled trials and one meta-analysis. Moreover, data from 19 prospective studies, one retrospective study and four other articles were used. Totally 44 scientific articles are included, involving 11,289 patients. The conclusions reached can be summarized into the following points: Primary treatment of patients with symptomatic B-CLL is recommended to be an oral alkylating agent such as chlorambucil. This drug induces tumour remission and symptomatic relief in a majority of patients with progressive disease. Response may be long-lasting, but cure is not obtained. Optimum dose and schedule of administration of chlorambucil or other alkylating agents have not been defined. It is recommended to defer initial therapy until required by disease progression. Large randomised trials have demonstrated that early treatment with chlorambucil in a continuous or an intermittent schedule does not prolong survival in B-CLL patients with low tumour burden (Binet stage A). The addition of corticosteroids to alkylator regimens has not been proven to give any benefit. Combination chemotherapy as primary treatment has not shown any advantage compared with single drugs. Early inclusion of anthracyclines to the therapy does not convincingly add to the activity of alkylating agents. The purine analogues fludarabine and 2-chlorodeoxyadenosine are active in B-CLL. However, like other drugs, they do not appear to be curative. In randomised multicentre trials a benefit from fludarabine as primary therapy compared with polychemotherapy (CHOP or CAP) has been observed in terms of tolerance and treatment response but not yet in survival. No randomised studies have been performed to show whether one of the purine analogues should be preferred. At relapse after single drug treatment, retreatment with the same drug often induces new remissions. However, the proportion of patients responding declines each time chlorambucil or any other single agent is readministered. At progression on single alkylating agents, the purine analogues or various combinations, mostly CHOP, frequently induce tumour remissions. For patients with advanced B-CLL failing to respond to fludarabine or CHOP, the prognosis is poor. None of the salvage regimens reported has produced durable remissions. High-dose chemo-radiotherapy with stem cell transplantation has been evaluated for young patients with B-CLL. A long survival has been shown in some patients following allogeneic and autologous transplantation. However, the risk of transplantation-related mortality is still high with allo-transplants and relapse is common after auto-transplantation. A benefit of purging autologous stem cells has been proposed but evidence is lacking. Thus, transplantation remains experimental; more patients and a longer follow-up are needed to assess if cure can be achieved. In the future an individual risk-adapted therapy will be required. The clinical heterogeneity of the disease has pointed to the necessity of new predictors for prognosis evaluated in prospective trials.

A patient exposed to thorotrast angiography developed sarcoidosis 21 years after the injection and myelofibrosis 13 years later. On the latter occasion an extreme deficiency in circulating lymphocytes forming rosettes with sheep erythrocytes (T-cells) was observed and a large fraction of the cells had chromosomal aberrations. Acute leukaemia developed 1 year later. The multiple clinical symptoms may be related to radiation-induced destruction of bone marrow tissue, mutations in haemopoietic cells and depression of cell-mediated immunity.

Seamen constitute a special group of international travellers who may run an increased risk of contracting hepatitis, because of visits to foreign ports and the particular environment on board ship. The purpose of the survey was to assess the prevalence of serological markers for hepatitis A, B and C virus infection among seamen and to identify present and previous risk factors for infection. 515 seamen were studied. The prevalence of antibodies against hepatitis A was 0.3% in subjects below 40 years of age, increasing with age above 40 years, and highest among those who had sailed in international trade. The prevalence of antibodies against hepatitis B was 2.7% in subjects below 40 years of age, increasing to 35.7% in the group above 60 years of age. Hepatitis C antibodies occurred in 1.2%. Vaccination of sailors against hepatitis A should follow the same recommendations as to other travellers. The prevalence of hepatitis B was higher than in reference groups of non-seamen but, because hepatitis B is only one of many blood-borne diseases, prevention should be directed towards changes in behaviour rather than vaccination, except for special groups. Young seamen in international trade were found to be most at risk of contracting sexually transmitted diseases.

PURPOSE: To study how objectively recorded mouse and keyboard activity affects distal arm pain among computer workers. METHODS: Computer activities were recorded among 2,146 computer workers. For 52 weeks mouse and keyboard time, sustained activity, speed and micropauses were recorded with a software program installed on the participants' computers. Participants reported weekly pain scores via the software program for elbow, forearm and wrist/hand as well as in a questionnaire at baseline and 1-year follow up. Associations between pain development and computer work were examined for three pain outcomes: acute, prolonged and chronic pain. RESULTS: Mouse time, even at low levels, was associated with acute pain in a similar way for all the examined regions. There were no exposure-response threshold patterns. Keyboard time had no effect. Mouse and keyboard sustained activity, speed and micropauses were not risk factors for acute pain, nor did they modify the effects of mouse or keyboard time. Computer usage parameters were not associated with prolonged or chronic pain. A major limitation of the study was low keyboard times. CONCLUSION: Computer work was not related to the development of prolonged or chronic pain. Mouse time was associated with acute distal arm pain, but the impact was quite small.

Epidemiological studies indicating that exposure to organic solvents is a risk factor for haematological malignancies are reviewed. Exposure to benzene is a risk factor for ANLL. A preleukaemic phase with pancytopenia is common and may be associated with a normo- or hypercellular marrow with morphological characteristics suggesting MDS. There are indications that other organic solvents than benzene may be leukaemogenic. Certain chromosome aberrations are characteristic in leukaemic cells from solvent exposed ANLL patients. The average latency time from start of occupational exposure until diagnosis is about 10-11 years. There is epidemiological evidence that exposure to organic solvents may also increase the risk of lymphoproliferative malignancies, i.e. ALL, NHL, HD and myeloma.

With a common study protocol, case-referent studies within cohorts were performed in Denmark, Norway, Sweden, and Finland to study reproductive hazards of women doing dry-cleaning work. Due to national differences not all of the studies could follow exactly the same procedures in data collection, but they were all based on the linkage of cohorts of dry-cleaning and laundry workers to national registers of births and reproductive failures. Summary measures from each study were combined without the data being pooled. The most significant finding was an increased risk of spontaneous abortion among the most exposed women in the Finnish data. This finding was only supported by the results of the other studies to a minor degree, and the combined odds ratio had confidence limits which included unity.

Previous studies identified serine, cysteine and metalloproteases in normal aqueous humours (AH) and suggested that a balance between proteases and their inhibitors may play a role in the modulation of the AH outflow. We aimed to determine whether secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor, is present in AH of patients with cataract and other eye pathologies. AH was collected from 117 cataract patients of which 55 were diagnosed with more when one eye disease: cataract only (n=62), pseudoexfoliation (PEX) (n=26), glaucoma (n=6), diabetes retinopathy (n=4), iritis-uveitis (n=4) and macular degeneration (n=28). The total protein in AH was determined by a Bradford assay and SLPI was analyzed by Western blot and ELISA methods. The average concentration of total protein and SLPI in AH samples was 160+/-15 microg/ml (n=117, +/-SEM) and 500+/-94 pg/ml (n=105), respectively. The cataract patients with additional eye disease(s) showed higher protein levels (201+/-35 microg/ml) than cataract (controls) (128+/-31 microg/ml), P

Background The aim of this study was to examine relations between computer work aspects and elbow and wrist/hand pain conditions and disorders. Methods In a 1-year follow-up study among 6,943 technical assistants and machine technicians self-reported active mouse and keyboard time, ergonomic exposures and associations with elbow and wrist/hand pain were determined. Standardized clinical examinations were performed among symptomatic participants at baseline and at follow-up. Results For continuous duration of mouse time adjusted linear effects were statistically significant for all investigated pain conditions. For continuous duration of keyboard time the corresponding effects were statistically significant for wrist/hand pain conditions except incident ‘severe’ wrist/hand pain. There were no threshold effects above 0 hr per week (hr/w) of mouse exposure in association with pain conditions, while keyboard exposure showed a threshold effect with 12-month wrist/hand pain at follow-up. Clinical diagnoses were not associated with exposure. Conclusions Detailed examination of self-reported exposures showed that mouse and keyboard time predicted elbow and wrist/hand pain from low exposure levels without a threshold effect, but mouse and keyboard time were not predictors of clinical conditions. Am. J. Ind. Med. 46:521–533, 2004. © 2004 Wiley-Liss, Inc.

OBJECTIVES: To investigate whether tingling/numbness of the hands and fingers among computer users is associated with elevated vibration threshold as a sign of early nerve compression. METHODS: Within the Danish NUDATA study, vibratory sensory testing with monitoring of the digital vibration threshold at seven frequencies on the second and fifth fingers of both hands was performed on 20 cases with unilateral tingling/numbness in the hands and fingers, and 20 gender- and age-matched controls. Both cases and controls were identified from questionnaire information about tingling/numbness at least once a week or daily within the last 3 months. Participants with more than slight muscular pain or disorders of the neck and upper extremities, excessive alcohol consumption, previous injuries of the upper extremities, or concurrent medical diseases were excluded. The two groups had a similar amount of work with mouse, keyboard, and computer. RESULTS: Seven of the 20 cases (35%) had elevated vibration thresholds, compared with 3 of the 20 controls (15%); this difference was not statistically significant (chi2=2.13, P=0.14). Compared with controls, cases had increased perception threshold for all frequencies, but the difference was statistically significant for only 2 out of 14 measurements. Comparison between left and right hand threshold values within the case group did not show any significant difference at any frequency. CONCLUSIONS: The results indicate that tingling/numbness of the hands and fingers among computer users cannot be explained by nerve compression

Staging of patients with lung cancer to determine operability is intended to efficiently limit futile thoracotomies without denying possibly curative surgery. Currently available staging tests are imperfect alone and in combination. Imaged suspected metastases often require tissue confirmation before surgery can be denied. Endoscopic ultrasound (EUS) may help identify inoperable patients by providing tissue proof of inoperability in a single staging test, with similar sensitivity for identifying inoperable patients as other staging tests. Therefore, we compared computed tomography, positron emission tomography (PET), and EUS with fine-needle aspiration under conscious sedation, each test interpreted blinded with respect to the other tests, for identifying inoperable patients in a consecutive cohort of 79 potentially operable patients with suspected or proven lung cancer. An economic analysis was also performed. Thirty-nine patients were found inoperable (a 40th patient's inoperability was missed by all preoperative staging tests). The sensitivity of computerized tomography was 43%. PET and EUS each had similar sensitivities (68 and 63%, respectively) and similar negative predictive values (64 and 68%, respectively), but EUS's superior specificity (100 vs. 72% for PET) and considerably lower expense means it may be preferred to PET early in staging to identify inoperable patients.

ContextComputer use is increasingly common among many working populations, and concern exists about possible adverse effects of computer use, such as carpal tunnel syndrome (CTS).ObjectivesTo estimate the prevalence and incidence of possible CTS and to evaluate the contribution of use of mouse devices and keyboards to the risk of possible CTS.Design and SettingA 1-year follow-up study with questionnaires conducted in 2000 and 2001 at 3500 workplaces in Denmark, followed on each of the 2 occasions by a clinical interview on symptom distribution and frequency.ParticipantsThe questionnaire was sent to 9480 members of a trade union, with an initial response rate of 73% (n = 6943), and 82% (n = 5658) at follow-up.Main Outcome MeasuresAt baseline, there were 3 outcome measures: tingling/numbness in the right hand once a week or more as reported in the questionnaire; tingling, numbness, and pain in the median nerve in the right hand confirmed by clinical interview; and tingling, numbness, and pain in the median nerve in the right hand at night confirmed by clinical interview. At 1 year of follow-up the main outcome of interest was onset of symptoms among participants who had no or minor symptoms at baseline.ResultsThe overall self-reported prevalence of tingling/numbness in the right hand at baseline was 10.9%. The interview confirmed that prevalence of tingling/numbness in the median nerve was 4.8%, of which about one third, corresponding to a prevalence of 1.4%, experienced symptoms at night. Onset of new symptoms in the 1-year follow-up was 5.5%. In the cross-sectional comparisons and in the follow-up analyses, there was an association between use of a mouse device for more than 20 h/wk and risk of possible CTS but no statistically significant association with keyboard use.ConclusionsThe occurrence of possible CTS in the right hand was low. The study emphasizes that computer use does not pose a severe occupational hazard for developing symptoms of CTS.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for indolent non-Hodgkin's lymphoma (NHL), predominantly follicular lymphoma, is based on 108 scientific reports including 31 randomised studies, 38 prospective studies and 18 retrospective studies. These studies involve 8,699 patients. The conclusions reached can be summarized into the following points: In initially localized disease-- The addition of chemotherapy to radiotherapy as primary treatment has not convincingly prolonged remission duration or survival. In initially advanced disease-- Alkylating agents are useful palliative treatment options which can result in improved well-being for most patients, often for long periods. Combinations of chemotherapy have not convincingly resulted in more or longer remissions. There is no proof that initial combination chemotherapy will prolong survival in comparison with single drugs. The addition of interferon to initial combination chemotherapy may increase the response rate, significantly prolong remission duration, but prolonged survival has not been unequivocally proven. In the absence of disease-related symptoms, treatment can safely be deferred. For patients with relapsed lymphoma-- Patients may repeatedly respond to alkylating agents or combinations containing an alkylating agent, although the proportion responding decreases with each relapse. Patients relapsing after or who are refractory to treatment with alkylating agents often respond to treatment with combinations containing an anthracycline. Responses are also often seen in patients treated with purine analogues alone or in combination with other drugs. High dose chemotherapy followed by autologous or allogeneic reestablishment of bone marrow function can induce long-term remissions but it is not proven whether they are more frequent or of longer duration than with conventionally dosed therapy. The impact of the novel treatment strategies including high-dose therapy on overall survival is still uncertain. A monoclonal antibody, rituximab, is a new active substance for patients with relapsed lymphoma. It can induce remissions also in chemoresistant patients.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on aggressive, high grade non-Hodgkin's lymphoma (NHL), chiefly diffuse large B-cell lymphomas, is based on 111 scientific articles, including 35 randomised trials, 44 prospective studies and 11 retrospective studies, including totally 21,830 treated patients. The conclusions reached can be summarised into the following points: For patients with localised aggressive NHL (stage I and non-bulky II) a combination of chemo- and radiotherapy will result in cure for a large proportion of patients. For a subgroup of patients with stage I non-bulky disease and without risk factors, local radiotherapy alone is also adequate treatment. For patients with disseminated aggressive NHL, including the elderly, the CHOP-regimen remains the standard primary chemotherapy. In an unselected population, this treatment cures about one third of the patients. For most patients with poor prognostic factors, CHOP provides insufficient results. The results of therapy with dose-intensive combinations of cytotoxic drugs have been conflicting. Most randomised studies, using intensive regimens as first line therapy, have failed to show any benefit in comparison to CHOP. However, it is possible that regimens other than CHOP might be more beneficial in subgroups with 'high risk' disease. This remains to be investigated in prospective studies. In young, poor prognosis, patients a further intensified induction therapy requiring haematopetic stem cell support, i.e. high dose therapy, has been suggested to be beneficial. The best results have been reported from studies with full course standard induction followed by high-dose therapy. However, the study data are conflicting, which is why additional controlled studies are recommended. In patients refractory to or relapsing after initial therapy, different chemotherapy combinations may induce a new response. The responses are, however, rather short-lived and long-term survival is rarely seen. In patients not attaining complete remission after initial standard therapy, high-dose therapy with stem cell support may improve the response, but the impact on survival is not established. In patients refractory to initial standard therapy there is no evidence for a survival prolongation from high-dose therapy with stem cell support, although a subset of patients might benefit. For patients with chemosensitive relapse, salvage therapy followed by high-dose therapy with stem cell support is recommended, since this may result in prolonged survival.

The purpose of this study was to estimate the minimal magnitude of the HIV problem among seafarers in Denmark. The material is based on case records from the 6 medical departments in Denmark that undertake treatment of HIV patients. Retrospectively, all case records of HIV infection among seafarers - and of their sexual contacts - have been identified. 33 seafarers with HIV infection or AIDS were identified; 17 had no other known risk factor than heterosexual contacts in high-endemic areas. These results show that HIV infections have entered into the heterosexual group of seafarers. HIV-infected seafarers are a risk group for carrying HIV infection into the heterosexual population in non-endemic areas. In 5 known cases, this has actually taken place in Denmark. The majority of the heterosexually infected seafarers were probably infected early in the AIDS era. We do not know if Danish seafarers are still acquiring HIV abroad.

Using a self-report questionnaire, the Hospital Anxiety and Depression (HAD) scale, feelings of anxiety and depression were assessed in 133 breast cancer patients referred for adjuvant radiotherapy following surgical treatment. Eighteen patients (14%) had scores indicating morbid anxiety. Significant depression was recorded for only 2 patients (1.5%). Severe anxiety was recorded for 10 out of 54 mastectomized patients (19%) and for 8 out of 79 patients treated with breast conserving surgery (10%). The difference was not significant (p = 0.13). In a subgroup aged 50-59 years, morbid anxiety was significantly more common among mastectomized patients than among patients operated conservatively, 4 out of 9 (44%) vs. 1 out of 23 (4%) (p = 0.01). Such a pattern was not discernable in the patients50 years of age or thoseor = 60 years old. The results suggest that, at start of adjuvant radiotherapy, emotional distress is characterized by anxiety rather than depression and the risk of morbid anxiety is especially large for mastectomized women in their fifties.

The chromosome banding pattern was determined in a series of 30 untreated adult patients with acute non-lymphocytic leukemia. A significant correlation was found between survival time and the presence of chromosomal abnormality in the bone marrow at the time of diagnosis. The median survival time from diagnosis to death was 8.0 months for patients with only normal metaphases, 2.5 months for patients with a mixture of normal and abnormal cells, and 1.0 months for patients with abnormal metaphases only. Although the 3 groups of patients showed a wide range of survival time, the results indicate that karyotype analysis by means of modern cytogenetic techniques is an important prognostic indicator in acute leukemia. It is suggested that in patients with abnormal bone marrow cells the disease has reached a more advanced stage than in those with exclusively normal diploid cells.

A group of 18 patients with acute nonlymphocytic leukemia and the chromosomal aberration monosomy 7 in their bone marrow cells was compared to a group of control patients with the same disease but normal bone marrow chromosomes. The monosomy 7 group of patients had a higher incidence of fever and infections, and a higher white blood cell and granulocyte count compared to the control group at the time of diagnosis. The clinical difference between the groups continued over the first month of hospitalization. Complete remission was obtained in 12% of the monosomy 7 group and in 59% of the control group. Survival was clearly longer in the control group of patients. Monosomy 7 of the bone marrow in acute nonlymphocytic leukemia is therefore to be considered a bad prognostic sign.

A cytogenetic study, including prophase-prometaphase chromosome analysis, of a patient with EBV-genome-negative acute lymphocytic leukemia of B-cell type with Burkitt-type cells is presented. All bone-marrow mitoses examined had a 14q + marker chromosome which was identified as a reciprocal 8;14 translocation of exactly the same type as in Burkitt's lymphoma.

The chromosome banding pattern was analyzed in bone-marrow cells and/or spleen cells of 10 patients in the blastic phase of chronic myeloid leukemia (CML). It was obvious from the karyotype analysis that the chromosome aberrations occurring addition to the Philadelphia chromosome (Ph1) were strictly non-random. An extra Ph1, trisomy 8 and/or trisomy for the long arm of chromosome 17 were observed in all cases. This consistent pattern of chromosome involvement in CML was confirmed in 57 cases from the literature studied with banding techniques. In 88% of the total number of cases with further changes at least one of the three main chromosomal aberrations was found ("major route" of karyotypic evolution).

Results of epidemiologic studies indicating an association between solvent exposure and the development of malignancies affecting haematopoietic and lymphatic tissues are reviewed. Clinical and cytogenetic data supporting this association are discussed. A variety of malignant disorders have been associated with solvent exposure, i.e. acute leukaemia, Hodgkin's disease (odds ratio 2.8-6.6), non-Hodgkin's lymphoma (odds ratio 3.3) and myeloma, and there are some indications that solvent exposure may be a risk factor for myelofibrosis. The carcinogenic effect of benzene is epidemiologically and experimentally well documented and there are some indications that other solvents may also be hazardous. Possible mechanisms bringing about malignant transformation are discussed. The need for further epidemiologic, cytogenetic and clinical studies on the association between solvent exposure and malignant diseases is emphasised.

In an attempt to determine the frequency of liver injury in adult cœliac disease (A.C.D.) the case records of 74 consecutive patients were examined. In 13 cases histological sections of the liver were available and in 5 of these there were signs of reactive hepatitis. Histological signs of distinct hepatic injury with cirrhosis and/or chronic active hepatitis were found in 7 other patients. In 5 of these serum-IgA was normal, whereas 16 out of 20 control patients with liver cirrhosis not associated with A.C.D. had raised serum-IgA. Serum-aspartate-aminotransferase and serum-alanine-aminotransferase were determined in 53 patients; 29 had raised concentrations. In 19 patients serum-aminotransferases were repeatedly determined before and during the dietary regimen and there was a significant reduction in enzyme concentrations during treatment. The median concentration of serum-alkaline-phosphatase was also reduced during treatment but not significantly. The histological evidence of liver injury in 16% and the abnormal liver-function tests in 39% of the patients indicate that hepatic injury is common in A.C.D. Since liver-function tests or liver biopsy specimens were available for only about two-thirds of the patients, liver damage in A.C.D. may be more common than indicated by these results. The effect of a gluten-free diet on aminotransferase concentrations indicates that the liver injury may be reversible and suggests that in some A.C.D. patients progressive liver damage may be prevented by suitable treatment. Since A.C.D. is not always recognised, the diagnosis should be considered in patients with liver disease of unknown aetiology.

The karyotypic pattern in 69 patients with Ph1-positive chronic myeloid leukaemia (CML) was investigated during the blastic phase (BC) and correlated with survival and certain parameters of potential prognostic significance, including blast morphology, basophilia and thrombocytopenia. There was no difference in median survival in BC between patients with and without aberrations in addition to the Ph1. Nor were there any differences in this respect among patients with the specific aberrations +Ph1, +8, iso(17q), or other abnormalities. There was no correlation between the incidence of thrombocytopenia and any particular karyotypic change. However, the incidence of basophilia was a characteristic feature for patients with an iso(17q). The survival time in BC was considerably longer in patients with a lymphoid morphology of the blastic cells compared to the myeloid varieties, and within the myeloid varieties the survival in BC was longer in patients with granular differentiated blasts than in those with granular atypical blast cells. No obvious correlation was apparent between blast morphology and karyotypic pattern. However, a pattern was discernible regarding survival and certain chromosomal changes within some morphologic groups: in patients with granular differentiated and lymphoid morphology, the median survival in BC was considerably longer when the bone marrow cells had a Ph1 as the sole abnormality compared to patients who had additional aberrations.

Thymidine labelling indices (LI) and the number of clonal chromosome aberrations were assessed in fine-needle aspirates from enlarged lymph nodes in 22 patients with non-Hodgkin's lymphoma (NHL). 11 patients had LI greater than 3.0 (median 8.4) and 11 others had LI less than 3.0 (median 1.0). Three categories of chromosome aberration were recorded: normal karyotype, 1-5 aberrations, and greater than or equal to 6 aberrations or multiple complex changes. The distribution of these categories was different among the patients with LI greater than 3.0 compared to those with LI less than 3.0 (p = 0.02). 8 of 11 patients with LI greater than 3.0 had greater than or equal to 6 or complex changes. The corresponding figures for patients with LI less than 3.0 were 2 out of 11. When 16 previously untreated patients were analysed separately, the median number of clonal aberrations was 6.5 in 8 patients with LI greater than 3.0 and 2.5 in 8 others with LI less than 3.0 (p = 0.025). The results suggest that early and spontaneous changes in the genetic material are common in lymphomas with a high proliferative activity. According to previous studies, therapeutic results are especially poor in NHL with high LI. It is proposed that a high proliferative activity of lymphoma cells facilitates an early development of several new mutants and that some of these may be resistant to chemotherapeutic agents.

Chromosome analysis of lymphoma cells was performed in 54 untreated patients with non-Hodgkin's lymphoma (NHL). 10 patients had a history of daily occupational handling of organic solvents for at least 1 year (exposed group) and 44 patients had never (or only for shorter periods) worked with solvents (unexposed group). There were no differences between exposed and unexposed patients regarding age, clinical stage or histologic malignancy grade. The patients were assigned to three categories: Patients with 0-4, 5-9, or greater than or equal to 10 cytogenetic events producing clonal aberrations of the lymphoma cells. The proportions of exposed patients in these categories were 2/26 (8%), 5/20 (25%) and 3/8 (38%); respectively, i.e. with increasing numbers of events there was an increasing probability of previous exposure to solvents (p = 0.035, trend analysis). 5 of 7 exposed patients (71%) with intermediate or high-grade lymphomas displayed translocations involving the band 14q32. Such 14q+ markers were found in only 5 out of 28 unexposed patients (18%) with lymphomas of comparable malignancy grade (p = 0.01). Among unexposed patients with intermediate or high-grade lymphoma the most common clonal aberration was 6q- which occurred in 10 out of 28 patients (36%). This abnormality was not observed in the exposed patients with lymphomas of corresponding malignancy grades (p = 0.08). It thus appears that the number of clonal chromosome aberrations is especially large in NHL patients with a history of occupational exposure to organic solvents. Moreover, such exposure may be associated with characteristic cytogenetic changes in the lymphoma cells.

Investigations on the association between environmental hazards and the development of various types of leukaemia are reviewed. Regarding acute non-lymphocytic leukaemia (ANLL) exposure to ionizing radiation is a well-documented risk factor. According to several recent studies exposure to strong electromagnetic fields may be suspected to be of etiologic importance for ANLL. There is evidence that occupational handling of benzene is a risk factor and other organic solvents may also be leukaemogenic. Occupational exposure to petrol products has been proposed to be a risk factor although the hazardous substances have not yet been defined. Results of cytogenetic studies in ANLL suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. These results are of interest because it has been proposed that chromosomal rearrangements may play a role in the activation of cellular oncogens. Exposure in utero to ionizing radiation has been proposed to be a risk factor for acute lymphocytic leukaemia (ALL) in children. Unlike ANLL there seems at present to be little evidence that ALL is related to exposure to some chemicals. Chronic myeloid leukaemia (CML) may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance for the development of chronic lymphocytic leukaemia (CLL). According to some studies an abnormally high incidence of CLL may be found among farmers in the USA. These results have not been confirmed in Scandinavian studies. There seems to be little evidence that CML or CLL are related to occupational handling of some chemicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome banding pattern of bone marrow cells, cell morphology according to the FAB classification, and clinical findings were compared in two groups of adult patients with acute nonlymphocytic leukemia (ANLL): 52 patients occupationally exposed to chemical solvents, insecticides, or petrol products, and 110 patients with no history of occupational exposure to potential mutagenic/carcinogenic agents. Striking differences were found between the two groups: (1) Clonal chromosomal aberrations were present in 75% of exposed patients compared with only 32% in the nonexposed group. (2) Of the patients exposed to solvents and insecticides 92% had abnormal chromosomes, whereas only 29% of patients exposed to petrol products showed abnormalities; in the total material 10 13 exposed patients with normal chromosomes were exposed to petrol products. (3) The relationship between chromosomal abnormality and exposure was evident in both females and males. However, only 29% of women with an abnormal karyotype were exposed, whereas 70% of males with an abnormal karyotype were exposed. (4) The incidence of certain characteristic karyotypic abnormalities, i.e., −5 5 q − , −7 7 q − , +8, +21, t(8;21), and t(9;22), were decidedly more common in exposed than in nonexposed patients. At least one of these changes were present in 92% of exposed patients with aberrations, whereas in the nonexposed group the incidence was only 60%. (5) The monocytic varieties of ANLL (M4 + M5) were more common in the nonexposed patients, whereas erythroleukemia (M6) was more common in the exposed group. The predominance of abnormal karyotypes in the exposed compared to the nonexposed patients was similar in leukemia types M1 + M2 and in M4 + M5. (6) There was no difference in survival time between the two groups and the same correlation was obvious in both exposed and nonexposed patients: patients who had only abnormal metaphases had poorer prognosis than those with normal bone marrow metaphases only (6 vs 1.5 months). This correlation was obvious in patients classified as acute myeloid leukemia (AML) as well as in the monocytic varieties of ANLL.

In vitro studies have been done on haematopoietic cells from a patient with cyclic neutropenia characterized by severe depression of blood neutrophil levels every 21 days. Serial blood counts reveal periodic fluctuations in neutrophils, monocytes and reticulocytes. Agar culture of marrow cells shows normal concentration of colony forming cells. The percentage of colony forming cells in S phase is highly increased during profound neutropenia and normal during the recovery phase relating the granulocyte production to the peripheral neutrophil level. Studies of ingestion rate, bactericidal activity, lactate production and glucose oxidation during phagocytosis in isolated granulocytes show normal results. Also the ingestion rate in isolated monocytes is normal. Serial karyotype analyses of marrow cells during the neutrophil cycle display a normal pattern. Serum myeloperoxidase levels vary inversely with the peripheral neutrophil count indicating increased granulopoietic activity during profound neutropenia, which might be associated with non effective granulopoiesis during profound neutropenia, leading to a lack of granulocyte reserves in the marrow.

Patients with neurological disorders may have a reduced ventilatory response to a rising PaCO2. This is often unpredictable and may become apparent only when other complications, e.g. infections (pneumonia), occur or when the patient is subjected to general anaesthesia. This paper described a simple method suitable for screening patients who may have an impaired capacity of eliminating CO2 when stressed. Ventilatory changes were determined during the continuous recording of the CO2 concentration in end-tidal air in 20 healthy subjects, who were breathing first air and then gas mixtures containing 21% O2 and 2.5 or 5% CO2. A prediction interval with 90 and 95% probability limits was constructed for healthy individuals. The normally expected change in minute ventilation per m2 body surface area per change in PACO2 (delta versicle E/m2, l/min/delta PACO2, for this technique is also given.

In chronic myeloid leukaemia the adhesiveness of mature neutrophilic leukocytes to an approximately standardized glass bead column and the phagocytic activity of neutrophils are abnormally low. The distribution of neutrophils with different power of phagocytosis has been investigated in 6 cases of CML. The increasing number of white blood cells characteristic of aggravation of the disease is accompanied by an increasing part of mature neutrophils with low phagocytic activity. Neutrophils with high phagocytic activity do not change their number to any extent in different stages of CML. Nor does this number seem to be significantly higher in CML than in normals. Neutrophils in 3 cases of polycythaemia vera with leukocytosis, 1 case of thrombocythaemia with leukocytosis and 2 cases of 32P-treated polycythaemia vera with signs of acute leukaemia had a high phagocytic activity. One case of myeloproliferative disorder originally diagnosed as polycythaemia vera with certain later signs of CML had a phagocytic pattern similar to that seen in typical cases of CML.

In a case-control study based on 859 consecutive non-Hodgkin's lymphoma (NHL) cases identified through a tumor registry between 1990 and 1998, the authors collected demographic, occupational, exposure, and education information. Exposures were identified through self-report, reported occupational history, and the use of a job-exposure matrix. Conditional logistic regression analyses of the 859 cases and 1,310 controls showed increased risks in workers exposed to gasoline (odds ratio [OR] 1.46; 95% confidence interval [CI] 1.04, 2.05), aliphatic or alicyclic hydrocarbons (OR 1.75; CI 1.03, 2.99), aromatic hydrocarbons (OR 1.45; (CI 1.13, 1.86), and solvents for mole than five years (OR 1.59: CI 1.11, 2.28), as well as automobile mechanics (OR 1.82; CI 1.18, 2.81) and painters (OR 1.77; CI 1.13, 2.76). Exposures to pesticides and farming were not associated with increased risk. Prior radiotherapy was associated with increased risk (OR 2.84; (CI 1.85, 4.37). Concordance between analyses based on self-reported exposures, occupations, and the job-exposure matrix supported the links between organic solvents and prior radiotherapy and NHL but did not support associations between farming or pesticides and NHL.

Objectives Neck and shoulder pain and disorders were studied among frequent computer users, and the associated effect of mouse and keyboard use was evaluated. Methods Technical assistants and machine technicians were followed for 1 year. Questionnaires were sent to 9480 persons (initial response 73%, follow-up response 82%). Computer use information was obtained from the questionnaires. Symptom cases at baseline and follow-up were clinically examined using a standardized clinical protocol. The main outcomes were self-reported pain symptoms in the neck and right shoulder and clinical cases of rotator cuff syndrome, tension neck syndrome, and neck-shoulder pain with pressure tenderness. Results The prevalence of moderate-to-severe pain in the neck and right shoulder was 4.1% and 3.4%, respectively, and the 1-year incidence for no or minor baseline symptoms was 1.5% and 1.9%, respectively. At baseline, the prevalence rate ratio (PRR) for neck pain was 1.7 [95% confidence interval (95% CI) 1.1-2.6] for mouse use >25 hours/week, that for right shoulder pain increased from 1.6 (95% CI 1.1-2.4) for 15-19 hours/week to 2.5 (95% CI 1.4-4.3) for >30 hours/week of mouse use, and that for tension neck syndrome increased from 3.5 (95% CI 1.0-12) for 25-29 hours/week to 4.7 (95% CI 1.2-18) for >30 hours/week of mouse use . The relative risk (RR) for new neck pain was 1.8 (95% CI 0.8-3.9) for keyboard use 15 hours/week or more and increased to 2.4 (95% CI 0.8-6.8) for ≥30 hours/week or more. New right-shoulder pain symptoms were associated with mouse use >20 hours/week (RR 1.9, 95% CI 1.0-3.5, and RR 3.3, 95% CI 1.2-8.9) and with keyboard use >15 hours/week (RR 2.2, 95% CI 1.0-4.9). Conclusions Mouse use is associated with an increased risk of moderate-to-severe pain in the neck and right shoulder, and an association with tension neck syndrome is possible.