Requirements for estimation of doses from contaminants dispersed by a 'dirty bomb' explosion in an urban area.

The ARGOS decision support system is currently being extended to enable estimation of the consequences of terror attacks involving chemical, biological, nuclear and radiological substances. This paper presents elements of the framework that will be applied in ARGOS to calculate the dose contributions from contaminants dispersed in the atmosphere after a 'dirty bomb' explosion. Conceptual methodologies are presented which describe the various dose components on the basis of knowledge of time-integrated contaminant air concentrations. Also the aerosolisation and atmospheric dispersion in a city of different types of conceivable contaminants from a 'dirty bomb' are discussed.

Estimation of health hazards resulting from a radiological terrorist attack in a city.

In recent years, the concern for protection of urban populations against terror attacks involving radiological, biological or chemical substances has attracted increasing attention. It sets new demands to decision support and consequence assessment tools, where the focus has traditionally been on accidental exposure. The aim of the present study was to illustrate issues that need to be considered in evaluating the radiological consequences of a 'dirty bomb' explosion. This is done through a worked example of simplified calculations of relative dose contributions for a specific 'dirty bomb' scenario leading to atmospheric dispersion of 90Sr contamination over a city area. Also, the requirements of atmospheric dispersion models for such scenarios are discussed.

Performance of four clinical screening tools to select peri- and early postmenopausal women for dual X-ray absorptiometry.

Several methods to select postmenopausal women for dual X-ray absorptiometry (DXA) have been proposed. We decided to compare the performance of three clinical decision rules (SCORE, ORAI, OST) with the usual case-finding strategy based on the presence of a major risk factor for future fracture (CFMRF). The study subjects were 2009 healthy, white, peri- or early postmenopausal women participating in the Danish Osteoporosis Prevention Study (DOPS). DXA results expressed as T-scores and scores on SCORE, ORAI, OST and CFMRF were extracted from the DOPS database. First, we evaluated the screening tools as originally described by the developers. The resulting sensitivities and specificities ranged from 18% to 92% and from 66% to 85%, respectively. Only OST achieved a high sensitivity (92%) with respect to femoral neck T-score < or = -2.5; however, the sensitivity with respect to lumbar spine T-score < or = -2.5 was only 51%. Next, the performance of the screening tools was evaluated against T-score < or = -2.0 (and T-score < or = -2.5) in at least one of the regions: femoral neck, total hip or lumbar spine. Using ROC curve analysis, we determined cut-offs yielding sensitivities as close as possible to 90%. The CFMRF and the ORAI tool were too coarse to yield 90% sensitivity. The performances of OST and SCORE were equal from a clinical perspective in that the sensitivities and the specificities varied from 89% to 94% and from 23% to 28%, respectively. The performance of CFMRF was no better than could be expected by chance, yielding a sensitivity of 19% and a specificity of 85%. Applying SCORE or OST 75% of the women would have to be referred for densitometry to identify 90% of the women with T-score < or = -2.0 (or T-score < or = -2.5) in at least one region. In conclusion, our results question the utility of all the evaluated tools for screening peri- and early postmenopausal women for low BMD. However, if a decision on referral has to be made, it may be based on the simple OST rule, which performed as well as or better than any of the other tools.

Comparison of quantitative ultrasound and dual X-ray absorptiometry in estrogen-treated early postmenopausal women.

Identifying individuals at risk of developing osteoporosis is important in order to initiate early treatment. Many new techniques have been proposed as alternatives for DXA-scanning. Some of these alternatives certainly have advantages, but none have so far been demonstrated to predict fractures better, or even to identify individuals at risk of osteoporosis as well as with the standard method. In this study, comprising a group of women from the Danish Osteoporosis Prevention Study, we wished to investigate whether a technique based on quantitative ultrasound (QUS) could identify individuals with low BMC/BMD as measured by dual X-ray absorptiometry (DXA). Furthermore, we wished to test whether the method could detect differences between untreated individuals and those treated with hormone replacement therapy. We found that QUS could detect differences between the treated and untreated groups, but it was unable to identify women with low BMD, although it might be able to identify persons not at risk of osteoporosis. Low QUS values should be followed by a regular DXA measurement to confirm the presence of osteoporosis.

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study.

OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. RESULTS: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years. CONCLUSIONS: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.

Combined versus sequential hormonal replacement therapy: a double-blind, placebo-controlled study on quality of life-related outcome measures.

BACKGROUND: To compare combined and sequential hormonal replacement therapies to each other as well as placebo in patients suffering from the postmenopausal syndrome. Clinical outcomes were measured concerning both the specific postmenopausal symptoms (using the Kupperman scale) and health or well-being dimensions (using subscales of the General Health Questionnaire and specific depression and anxiety scales). METHODS: A prospective randomized double-blind study over 12 months of 105 normal early postmenopausal women in the setting of a general hospital. RESULTS: Both hormone replacement therapies were superior to placebo on the Kupperman scale (sweating, hot flushing, myalgia and vertigo). The psychic symptoms on the Kupperman scale were psychometrically invalid. However, psychic symptoms as measured by the Beck Depression Inventory and the General Health Questionnaire were significantly improved by the hormonal replacement therapies. No differences were observed when combined therapy was compared to sequential therapy. CONCLUSION: One-year treatment with hormonal replacement therapy is superior to placebo in measuring the somatic and psychic symptoms of the menopausal syndrome. No differences were found in this respect between combined and sequential replacement therapy.

Effect of 10 years' hormone replacement therapy on bone mineral content in postmenopausal women.

The purpose of this study was to investigate the effects of 10 years of hormone replacement therapy (HRT) in postmenopausal women on bone mineral density of the lumbar spine (L-BMD) and bone mineral content of the distal forearm (F-BMC). A total of 151 women were enrolled in the study, 100 of whom were randomized to receive oral HRT (equally divided between a continuous combined and a sequential treatment regimen), with the remaining 51 receiving placebo or no treatment. The study was double-blind for the first 24 months, followed by 8 years of open-label follow-up. Total treatment duration was 10 years. At the end of 10 years, 38% of women randomized to continuous combined HRT remained on therapy compared with 22% of those who had received sequential HRT and 49% of the untreated group. A further 18% of women originally randomized to HRT had switched to other regimens. After 10 years of therapy, L-BMD was found to be significantly higher in HRT-treated women than in those who remained untreated (14.5%; p < 0.001), corresponding to an increase in L-BMD of 13.1% from baseline values on HRT compared with a reduction in L-BMD of 4.7% without therapy. L-BMD increased by 15.9% in women receiving continuous combined therapy compared with 11.1% in those on sequential HRT; however, intergroup differences were not statistically significant. F-BMC decreased by 0.7% over the 10 year period in the HRT treatment groups compared with a reduction of 17.6% in untreated women (p < 0.001). Mean F-BMC was 20.3% higher in women who had received HRT than in those who had not received therapy at the end of the 10 year follow-up. In conclusion, 10 years of treatment with HRT resulted in a substantial increase in L-BMD, with F-BMC also significantly higher in the HRT group than in untreated women. These results confirm that long-term HRT exerts a continuous effect against bone loss in postmenopausal women.

[Differentiation of benign and malignant ovarian tumors by transluminal ultrasound scanning]. / Differentiering af benigne og maligne ovarietumorer med transabdominal ultralydskanning.

We intended to evaluate ultrasonographic criteria for differentiation of benign and malignant ovarian tumours, and to estimate the risk of malignancy in unilocular ovarian cysts. The files of 186 women aged 40 or above, who had undergone surgery in the department of gynaecology and obstetrics at Hillerød hospital between 01.01.1988-31.12.1990 and where pathological ovarian histology was found were reviewed. Preoperative ultrasonographic examination concerning size and morphology was compared to histological diagnosis. Tumours were classified according to the ultrasonographic internal structure into a) unilocular cysts, b) unilocular cysts with solid areas, c) multilocular cysts, d) multilocular cysts with solid areas and e) solid tumours. Criteria for suspicion of malignancy were unilocular cysts > 10 cm and complex and solid tumours, whereas smaller unilocular cysts were thought to be benign. Twenty-one tumours, diagnosed by ultrasound as unilocular cysts were all histologically benign, independently of size. For complex and solid tumors there was an increased risk of malignancy, and a statistically significant correlation between tumour size and risk of malignancy was found. Using the ultrasonographic criteria for malignancy a sensitivity of 97% and a specificity of 28% was found. The suggested criteria for ultrasonographic suspicion of malignancy were found usable in differentiating benign and malignant ovarian tumours. The risk of malignancy for unilocular cysts seems to be low, independently of size.

Continuous combined and sequential estradiol and norethindrone acetate treatment of postmenopausal women: effect of plasma lipoproteins in a two-year placebo-controlled trial.

OBJECTIVE: Our purpose was to examine the effects of postmenopausal estrogen therapy supplemented with progestogen on plasma lipoprotein levels. STUDY DESIGN: One hundred thirteen women were randomized to receive either placebo or a combination of 17 beta-estradiol and norethindrone acetate administered continuously (Kliogest) or sequentially (Trisequens). Plasma lipoprotein levels were measured at baseline and after 2 years of treatment and compared by analysis of variance. RESULTS: Hormone therapy lowered plasma cholesterol levels (p < 0.001) and low-density lipoprotein cholesterol (Kiogest, p < 0.001; Trisequens, p < 0.01), whereas high-density lipoprotein cholesterol levels were unchanged (Trisequens) or reduced (Kliogest, p < 0.01), primarily because of a decrease in the high-density lipoprotein-2 subfraction (p < 0.05). Low-density lipoprotein/high-density lipoprotein cholesterol ratios remained unchanged. CONCLUSIONS: Although hormonal replacement therapy with estradiol combined with norethindrone acetate eliminated the increase in high-density lipoprotein cholesterol levels observed with estrogen monotherapy, the reductions in low-density lipoprotein cholesterol concentrations still suggest reduced cardiovascular risk, according to the National Cholesterol Education Program and to recent observations indicating that risk is not necessarily inversely proportional to high-density lipoprotein cholesterol levels.

A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment.

A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered.

Popliteal valve incompetence and postoperative deep vein thrombosis.

In 79 patients undergoing hip or knee replacement surgery the preoperative condition of the popliteal vein valves was assessed by Doppler ultrasonography. Presence of postoperative deep vein thrombosis was determined by bilateral ascending phlebography seven to ten days after surgery. Antithrombotic prophylaxis consisted solely of TED stockings and early mobilization. The overall incidence of deep vein thrombosis was 20%. All thrombi were calf vein thrombi. One of these thrombi extended into the popliteal region and two into the femoral region. The incidence of deep vein thrombosis in patients with preoperative popliteal vein reflux when compared with patients with a normal popliteal valvular function was 55-15% (p less than 0.01). The incidence of deep vein thrombosis was also significantly lower in patients operated under epidural anaesthesia compared with patients under general anaesthesia. It is concluded that valvular incompetence of the popliteal vein predisposes to postoperative deep vein thrombosis.

Prediction of ovulation.

The purpose of this investigation was to evaluate all available ovulatory diagnostics with respect to sensitivity, specificity, diagnostic specificity (predictive value of a positive test, PVP) and diagnostic sensitivity (predictive value of a negative test, PVN). Twenty-one ovulatory women with more than 3 years of infertility problems were included in the study. PVP and PVN were highest for detection of urinary luteinizing hormone (LH) peak at ovulation (PVP = 90%, PVN = 95%) and for serum-estradiol peak 1 day before ovulation (PVP = 83%, PVN = 97%). The predictive values were lower for all other tests. The PVP (54%) and PVN (90%) were rather low for detection of ovulation with vaginal electric impedance. However, all ovulations were predicted when urinary LH peak and vaginal impedance were combined. Two women were stimulated with human chorionic gonadotropin to investigate a possible connection between the LH peak and the preovulatory vaginal electric impedance. No close connection between them could be demonstrated. Basal body temperature should not be used for the prediction of ovulation (PVP = 25%). We suggest that ovulation should primarily be predicted from the identification of the urinary LH peak and that other methods be supplementary.

Clinical versus ultrasonographic evaluation of scrotal disorders.

Clinical and ultrasonographic examinations of scrotal disorders were compared in 166 patients in order to determine their ability to distinguish between those diseases requiring surgery and those requiring clinical follow-up only. Ultrasound examinations were efficient in discriminating between normal and pathological findings. Extra-testicular lesions were readily differentiated from testicular ones. Although both clinical and ultrasonographic examinations had high sensitivity (90%) in detecting testicular cancer, the number of false positive findings was smaller after ultrasound examination. This gave a predictive value of a positive test of 53% after ultrasound examination but only 33% after clinical examination. Ultrasound examination may, therefore, reduce the number of surgical explorations in the scrotum and should be performed in patients with suspected testicular pathology based on history and palpatory findings.

A pilot study of natural radiation in Danish houses.

A pilot study was carried out to establish techniques and procedures for the measurement of indoor radiation in Denmark. A passive cup dosemeter was designed containing CR39 track detectors and TLD's to measure radon and external radiation, respectively. A total of 82 dwellings were selected covering most regions of the country. The dwellings were monitored in two three-month periods, one in winter and the other in summer. The average dose rate in air from external radiation was 0.09 muGy h-1. In the winter the average radon concentrations were 88 Bq m-3 and 24 Bq m-3 for single-family houses and flats, respectively; and in the summer the corresponding values were 52 Bq m-3 and 19 Bq m-3.

What do early bone scans tell about breast cancer patients?

In 1978, 1012 out of a total of 1888 Danish breast cancer patients registered for a nationwide therapeutical trial were bone-scanned to find osseous metastases. A re-reading group (N.R., O.M. and S.P.N.) interpreted 842 of the scans produced in the twelve participating hospitals. Specific criteria were used for grading the scintiscans. Of the 842 scans 682 were performed within 30 days of the operation and were defined as initial. The re-reading group found 50 (7%) of these scans to be equivocal and 46 (7%) to be indicative of bone metastases at the time of operation. The number of X-ray-verified bone metastases was only 5 (0.6%). The frequency of positive bone scans correlated with the age of the patients and tumor size, but not with clinical staging at the time of operation, number of positive axillary lymph nodes or degree of tumor anaplasia. Recurrences and death rates during a 2-yr follow-Up period correlated significantly with initial clinical staging. In the clinical low-risk group a positive initial bone scan worsened the prognosis, but this was not statistically significant for all patients grouped together. Although the prognostic value of the initial bone scan per se is dubious, it serves as a guidance for elective X-ray examination and as a basis for comparing subsequent scans.