The global burden of disease due to outdoor air pollution

As part of the World Health Organization (WHO) Global Burden of Disease Comparative Risk Assessment, the burden of disease attributable to urban ambient air pollution was estimated in terms of deaths and disability-adjusted life years (DALYs). Air pollution is associated with a broad spectrum of acute and chronic health effects, the nature of which may vary with the pollutant constituents. Particulate air pollution is consistently and independently related to the most serious effects, including lung cancer and other cardiopulmonary mortality. The analyses on which this report is based estimate that ambient air pollution, in terms of fine particulate air pollution (PM(2.5)), causes about 3% of mortality from cardiopulmonary disease, about 5% of mortality from cancer of the trachea, bronchus, and lung, and about 1% of mortality from acute respiratory infections in children under 5 yr, worldwide. This amounts to about 0.8 million (1.2%) premature deaths and 6.4 million (0.5%) years of life lost (YLL). This burden occurs predominantly in developing countries; 65% in Asia alone. These estimates consider only the impact of air pollution on mortality (i.e., years of life lost) and not morbidity (i.e., years lived with disability), due to limitations in the epidemiologic database. If air pollution multiplies both incidence and mortality to the same extent (i.e., the same relative risk), then the DALYs for cardiopulmonary disease increase by 20% worldwide.     

The big ban on bituminous coal sales revisited: serious epidemics and pronounced trends feign excess mortality previously attributed to heavy black-smoke exposure

The effect of banning bituminous coal sales on the black-smoke concentration and the mortality rates in Dublin, Ireland, has been analyzed recently. Based on the application of standard epidemiological procedures, the authors concluded that, as a result of the ban, the total nontrauma death rate was reduced strongly (-8.0% unadjusted, -5.7% adjusted). The purpose of this study was to reanalyze the original data with the aim of clarifying the three most important aspects of the study, (a) the effect of epidemics, (b) the trends in mortality rates due to advances in public health care, and (c) the correlation between mortality rates and black-smoke concentrations. Particular attention has been devoted to a detailed evaluation of the time dependence of mortality rates, stratified by season. Death rates were found to be strongly enhanced during three severe pre-ban winter-spring epidemics. The cardiovascular mortality rates exhibited a continuous decrease over the whole study period, in general accordance with trends in the rest of Ireland. These two effects can fully account for the previously identified apparent correlation between reduced mortality and the very pronounced ban-related lowering of the black-smoke concentration. The third important finding was that in nonepidemic pre-ban seasons even large changes in the concentration of black smoke had no detectable effect on mortality rates. The reanalysis suggests that epidemiological studies exploring the effect of ambient particulate matter on mortality require improved tools allowing proper adjustment for epidemics and trends. Aspects of harvesting and more recent results derived from a distributed lag model covering the effects of black smoke and temperature are also discussed.     

Increased cause-specific mortality associated with 2003 heat wave in Essen, Germany

During the 2003 heat wave an increase in mortality was observed in several European countries. Evidence suggests that the heat wave effect on mortality varies based upon underlying disease. In this study we examined the effects of the 2003 heat wave on all-cause and cause-specific mortality (neoplasms, cardiovascular and respiratory diseases) in a large west German city. Daily weather data for Essen was obtained from the German meteorological service. Death certificates for all deaths in Essen from 2002 to 2003 were coded according to the World Health Organization (WHO) guidelines. Mean numbers of daily deaths during and after the heat wave were compared with the average mortality in summer months (reference period). Poisson generalized additive models, adjusted for weekday and season, were fitted for overall and cause-specific mortality for the entire study period. During the 2003 heat wave (August 6-12), daily mortality increased by 15% (neoplasms), 30% (cardiovascular), and 61% (respiratory), with a decrease in the week after the heat wave of 17% for neoplasms and a sustained rise for respiratory mortality (77%). Regression analysis showed an association between heat and overall mortality in 2003 and greatest associations for respiratory mortality. Even the comparatively short heat wave in Essen in the year 2003 was associated with a rise in overall and cause-specific mortality. Different mechanisms appear to influence cause-specific mortality, with strongest associations for respiratory mortality. Harvesting might play a role in mortality due to neoplasms.     

Short-term effects of ambient (outdoor) air pollution on cardiovascular death in Tehran,Iran – a time series study

Abstract

The aim of this study was to estimate the effect of ambient air pollutants on cardiovascular deaths in Tehran, Iran. In this time series study, air pollutant data were acquired from the Environmental Protection Agency. Meteorological data were acquired from the meteorological organization, and death data were acquired from the Tehran’s cemetery registration. Generalized Additive Models (GAM) were used for estimating the Rate Ratio. NO₂, SO₂ and PM₁₀ were associated with total cardiovascular deaths. PM₁₀ and NO₂ showed stronger relations with deaths in the elder age group. The result of this study showed that NO_2, SO₂, PM₁₀ and O₃ are probably responsible for part of the cardiovascular deaths that happen daily in Tehran.     

Electrocardiographic changes during exposure to residual oil fly ash (ROFA) particles in a rat model of myocardial infarction.

Epidemiological studies have reported a positive association of short-term increases in ambient particulate matter (PM) with daily mortality and hospital admissions for cardiovascular disease. Although patients with cardiopulmonary disease appear to be most at risk, particulate-related cardiac effects following myocardial infarction (MI) have not been examined. To improve understanding of mechanisms, we developed and tested a model for investigating the effects of inhaled PM on arrhythmias and heart rate variability (HRV), a measure of autonomic nervous system activity, in rats with acute MI. Left-ventricular MI was induced in 31 Sprague-Dawley rats by thermocoagulation of the left coronary artery; 32 additional rats served as sham-operated controls. Diazepam-sedated rats were exposed (1 h) to residual oil fly ash (ROFA), carbon black, or room air at 12-18 h after surgery. Each exposure was immediately preceded and followed by a 1-h exposure to room air (baseline and recovery periods, respectively). Lead-II electrocardiograms were recorded. In the MI group, 41% of rats exhibited one or more premature ventricular complexes (PVCs) during the baseline period. Exposure to ROFA, but not to carbon black or room air, increased arrhythmia frequency in animals with preexisting PVCs. Furthermore, MI rats exposed to ROFA, but not to carbon black or room air, decreased HRV. There was no difference in arrhythmia frequency or HRV among sham-operated animals. These results underscore the usefulness of this model for elucidating the physiologic mechanisms of pollution-induced cardiovascular arrhythmias and contribute to defining the specific constituents of ambient particles responsible for arrhythmias.     

Do pollution time-series studies contain uncontrolled or residual confounding by risk factors for acute health events?

Acute health effects from air pollution are based largely on weak associations identified in time-series studies comparing daily air pollution levels to daily mortality. Much of this mortality is due to cardiovascular disease. Time-series studies have many potential limitations, but are not thought to be confounded by traditional cardiovascular risk factors (e.g., smoking status or hypertension) because these chronic risk factors are not obviously associated with daily pollution levels. However, acute psychobehavioral variants of these risk factors (e.g., smoking patterns and episodes of stress on any given day) are plausible confounders for the associations observed in time-series studies, given that time-series studies attempt to predict acute rather than chronic health outcomes. There is a fairly compelling literature on the strong link between cardiovascular events and daily "triggers" such as stress. Stress-related triggers are plausibly associated with daily pollution levels through surrogate stressors such as ambient temperature, daily workload, local traffic congestion, or other correlates of air pollution. For example, variables such as traffic congestion and industrial activity increase both stress-related health events and air pollution, suggesting the potential for classical confounding. Support for this argument is illustrated through examples of the well-demonstrated relationship between emotional stress and heart attack/stroke.     

GT-repeat polymorphism in the heme oxygenase-1 gene promoter is associated with cardiovascular mortality risk in an arsenic-exposed population in northeastern Taiwan

Inorganic arsenic has been associated with increased risk of atherosclerotic vascular disease and mortality in humans. A functional GT-repeat polymorphism in the heme oxygenase-1 (HO-1) gene promoter is inversely correlated with the development of coronary artery disease and restenosis after clinical angioplasty. The relationship of HO-1 genotype with arsenic-associated cardiovascular disease has not been studied. In this study, we evaluated the relationship between the HO-1 GT-repeat polymorphism and cardiovascular mortality in an arsenic-exposed population. A total of 504 study participants were followed up for a median of 10.7 years for occurrence of cardiovascular deaths (coronary heart disease, cerebrovascular disease, and peripheral arterial disease). Cardiovascular risk factors and DNA samples for determination of HO-1 GT repeats were obtained at recruitment. GT repeats variants were grouped into the S (< 27 repeats) or L allele (≥ 27 repeats). Relative mortality risk was estimated using Cox regression analysis, adjusted for competing risk of cancer and other causes. For the L/L, L/S, and S/S genotype groups, the crude mortalities for cardiovascular disease were 8.42, 3.10, and 2.85 cases/1000 person-years, respectively. After adjusting for conventional cardiovascular risk factors and competing risk of cancer and other causes, carriers with class S allele (L/S or S/S genotypes) had a significantly reduced risk of cardiovascular mortality compared to non-carriers (L/L genotype) [OR, 0.38; 95% CI, 0.16-0.90]. In contrast, no significant association was observed between HO-1 genotype and cancer mortality or mortality from other causes. Shorter (GT)n repeats in the HO-1 gene promoter may confer protective effects against cardiovascular mortality related to arsenic exposure.     

Acute health effects of ambient air pollution: the ultrafine particle hypothesis.

A strong and consistent association has been observed between adjusted mortality rates and ambient particle concentration. The strongest associations are seen for respiratory and cardiac deaths, particularly among the elderly. Particulate air pollution is also associated with asthma exacerbations, increased respiratory symptoms, decreased lung function, increased medication use, and increased hospital admissions. The U.S. Environmental Protection Agency (EPA) has recently promulgated a new national ambient air quality standard for fine particles, and yet the mechanisms for health effects at such low particle mass concentrations remain unclear. Hypotheses to identify the responsible particles have focused on particle acidity, particle content of transition metals, bioaerosols, and ultrafine particles. Because ultrafine particles are efficiently deposited in the respiratory tract and may be important in initiating airway inflammation, we have initiated clinical studies with ultrafine carbon particles in healthy subjects. These studies examine the role of ultrafines in: (1) the induction of airway inflammation; (2) expression of leukocyte and endothelial adhesion molecules in blood; (3) the alteration of blood coagulability; and (4) alteration in cardiac electrical activity. These events could lead to exacerbation of underlying cardiorespiratory disease. For example, airway inflammation may activate endothelium and circulating leukocytes, and induce a systemic acute phase response with transient hypercoagulability; this could explain the epidemiologic linkages between pollutant exposures and cardiovascular events. These approaches should be useful in identifying mechanisms for pollutant-induced respiratory and systemic effects, and in providing data for determining appropriate air quality standards.     

Indoor exposure to chemical and biological agents and health efects in primary school children

The aim of this study has been to estimate effects of indoor air pollutants on children’s health. An anamnestic retrospective study was done on 1074 children aged between 7 and 11 years old who lived in Nis (Serbia). An original questionnaire was used in an interview between training physicians and children’s parents. Interview data were processed by using Microsoft Excel and Epiinfo 6. The investigation determined that children who were more often exposed to combustion by-products had respiratory and nonspecific symptoms. Parental smoking was strongly associated with wheezing, bronchitis, headache and fatigue. There was no association between health and keeping pets, apart from partial nasal congestion. Presence of insects (e.g., cockroaches) and rats in households was a significant risk factor for all symptoms and diseases estimated except for asthma and pneumonia. Homes abundant in textiles were the cause of nasal congestion, wheezing and fatigue in children. Old mattresses were associated with respiratory symptoms, bronchitis, and nonspecific symptoms. It has been concluded that indoor air quality plays a major role in children’s health. Sources of indoor air pollution are present in every home. Being aware of the risks associated with indoor air quality problems, consequently, leads to their mitigation.     

Measuring progress in the management of ambient air quality: the case for population health

Although progress has been made in the last few decades at reducing ambient concentrations of air pollutants, scientific evidence suggests that there remains a risk to human health from exposure to these pollutants at current levels in Canada. Much of the motivation for air pollution reduction efforts is to protect population health. This article presents a method of monitoring changes in air pollution-related health outcomes over time in conjunction with temporal changes in ambient pollution concentrations. The progress measure is a function of temporal changes in location-specific ambient concentrations and the potentially time-dependent association between those concentrations and daily deaths. The progress measure can be determined for a single location or at a national level. The measure can also be extended to include several pollutants. The progress measure is illustrated with an example of how changes in nitrogen dioxide levels in 12 Canadian cities from 1981 to 1999 have translated into changes in the percent of nonaccidental mortality burden attributable to this pollutant over time.     

Air pollution and postneonatal mortality in a tropical city: Kaohsiung, Taiwan

With growing evidence of the association between daily mortality and air pollution in adults, it is important to investigate whether infants are also susceptible to the adverse health effects of ambient air pollutants. The purpose of this study is to examine the relationship between air pollution and postneonatal mortality in Kaohsiung, Taiwan, a large industrial city with a tropical climate, during the period 1994-2000, using a case-crossover analysis. Case-crossover analysis provides an alternative to Poisson time-series regression for studying the short-term adverse health effects of air pollution. The air pollutants examined included particulate matter (PM(10)), sulfur dioxide (SO(2)), ozone (O(3)), nitrogen dioxide (NO(2)), and carbon monoxide (CO). The risk of postneonatal deaths was estimated to increase by 4.0% per 67 microg/m(3) (the interquartile range in daily ambient concentration of PM(10)) for PM(10), 1.8% per 17.84 ppb for NO(2), 5.1% per 0.31 ppm for CO, and 4.6% per 19.20 ppb for O(3). Although positive, none of these associations achieved statistical significance. The established link between air pollution levels and infant mortality may not be as strong in cities with tropical climates, although other factors such as differences in pollutant mix or the underlying health of the postneonates may explain the lack of a strong association in this study. Further studies of this type in cities with varying climates and cultures are needed.     

Dietary micronutrients and gastric cancer: hospital based study

The association between micronutrients and gastric cancer is still unclear. The aim of this study is to determine the relationship between dietary intake of micronutrients and risk for gastric cancer. We used data from hospital-based case control study conducted at Clinical Centre Nis (Serbia) from 2005 and 2006. Patients (n=102) with first histologically confirmed gastric cancer and matched non-cancer patients (controls, n=204) were interviewed using structured questionnaire and FFQ (Food frequency questionnaire). Multivariate logistic regression analysis showed a significant positive association between gastric cancer and dietary intake of sodium (OR=6.22; 95%CI 1.99–7.86), but a significant negative association between potassium (OR 0.01; 95%CI 0.00–0.08), iron (OR 0.05; 95%CI 0.01–0.56), vitamin C (OR 0.05; 95%CI 0.01–0.38), vitamin E (OR 0.04; 95%CI 0.01–0.29) and niacin (OR 0.07; 95%CI 0.00–0.38) dietary intake. Intake of phosphorus, calcium, magnesium, zinc, retinol, β carotene, tiamin, vitamin B6, and folic acid was not significantly related to gastric cancer risk.     

Genetic bottleneck among daghestan highlanders migrating to lowlands

We present results of Short tandem repeat polymorphisms (STRPs) analysis and epidemiology study of indigenous ethnic highlanders of Daghestan and of the migrants from highlands to the lowland area in 1944, in comparison with native lowlanders. Results obtained show that demographically ancient highland ethnics have achieved a relatively stable equilibrium in their native environment and are characterized by optimal level of the main viability parameters (fertility, mortality, lifespan and morbidity). Migrants from highlands to the lowlands experienced dramatically increased morbidity and mortality in 1944–1947: up to 65–70% of total migrants had suffered malaria, typhus and other new infections and about 35–37% of total migrants had died. Genetic-epidemiological study support that non-survived migrants were characterized by a higher inbreeding rate, lower heterozygosity and higher physiological sensitivity to the environmental stress. This inter-connected complex had advantage for adaptation of the highlanders to the native environment but diminished their adaptability in the new and/or changing environment. A detailed study using STRP we performed in 1995–1999 in one highland isolate of ethnic Avars of whom about 50% were moved to the lowland area. We found significant differences in genetic and demographical structures between these highland and migrant parts of the isolate: the genetic bottleneck among migrants had a great qualitative and quantitative impact on their gene pool, i.e., lost of rare native population alleles, as well as of about 1/3 of total migrants with certain genotypes. Survived migrants demonstrate shorter lifespan and higher morbidity rate that support their still ongoing genetic adaptation to the lowland environment.     

Proceedings. Radioactivity in diet.

Male and female Syrian golden hamsters were exposed to the smoke of [¹⁴C]dotriacontane-16,17 ([¹⁴C]DOT)-labelled cigarettes in 2 different exposure systems. These 2 systems differed in terms of the smoke concentration drawn into the exposure chamber. To compare the effectiveness of the exposure systems, the inhaled dose of ¹⁴C-labelled cigarette smoke was determined in the different parts of the hamster respiratory tract by liquid scintillation counting. About 6 times more smoke particles were deposited in the respiratory tract after exposure to high smoke concentration with intermittent puffs of fresh air (closed system) than after exposure to smoke diluted with air (open system). About 80% of the diluted smoke reached the bronchi and lung compared to approximately 60% of the concentrated smoke. The remainder of the dose was trapped in the upper respiratory tract, mainly by the nose and larynx. Additionally, in the open system the total dose of inhaled smoke was dependent upon the position in the exposure chamber. The results are discussed with respect to the use of the exposure systems for chronic cigarette smoke inhalation studies in experimental respiratory tract carcinogenesis.     

Air Pollution and Postneonatal Mortality in a Tropical City: Kaohsiung,Taiwan

With growing evidence of the association between daily mortality and air pollution in adults, it is important to investigate whether infants are also susceptible to the adverse health effects of ambient air pollutants. The purpose of this study is to examine the relationship between air pollution and postneonatal mortality in Kaohsiung, Taiwan, a large industrial city with a tropical climate, during the period 1994–2000, using a case-crossover analysis. Case–crossover analysis provides an alternative to Poisson time-series regression for studying the short-term adverse health effects of air pollution. The air pollutants examined included particulate matter (PM₁₀), sulfur dioxide (SO₂), ozone (O₃), nitrogen dioxide (NO₂), and carbon monoxide (CO). The risk of postneonatal deaths was estimated to increase by 4.0% per 67 μg/m³ (the interquartile range in daily ambient concentration of PM₁₀) for PM₁₀, 1.8% per 17.84 ppb for NO₂, 5.1% per 0.31 ppm for CO, and 4.6% per 19.20 ppb for O₃. Although positive, none of these associations achieved statistical significance. The established link between air pollution levels and infant mortality may not be as strong in cities with tropical climates, although other factors such as differences in pollutant mix or the underlying health of the postneonates may explain the lack of a strong association in this study. Further studies of this type in cities with varying climates and cultures are needed.     

Effects of memantine, haloperidol, and cocaine on primary and conditioned reinforcement associated with cocaine in rhesus monkeys

Rationale The N-methyl-d-aspartate (NMDA) receptor has been implicated in mediating the reinforcing effects of abused drugs. Some reports indicate the uncompetitive NMDA antagonist, memantine, modulates the conditioned and unconditioned effects of stimulants in rats. Objective The objective of this study was to evaluate the effects of memantine on the primary and conditioned reinforcing effects of cocaine in the rhesus monkey. Methods Rhesus monkeys were trained to press levers reinforced with either cocaine-associated stimuli (brief stimuli, BS) or 30-μg/kg cocaine infusion during daily, 75-min experimental sessions in which the reinforcers were independently available in separate components according to identical progressive ratio (PR) schedules. Memantine (0.3–10 mg/kg), and as comparators, haloperidol (0.001–0.1 mg/kg) and cocaine (0.01–1 mg/kg), were administered 5 min before experimental sessions. Results Memantine (0.3–3 mg/kg) produced decreases in responding maintained by BS presentations at some doses which failed to affect cocaine self-administration when measured during equivalent periods early in the experimental session. Memantine (3 mg/kg) increased cocaine self-administration, however, later in the session. A low dose of haloperidol (0.001 mg/kg) increased the number of BS presentations, whereas higher doses decreased their number. Cocaine self-administration was not significantly affected by haloperidol until a behaviorally suppressant dose (0.1 mg/kg) was administered. Pretreatment with high doses of cocaine (0.3 and 1 mg/kg) decreased responding maintained by both reinforcers. Conclusion These results suggest that while memantine may attenuate the conditioned reinforcing effects of cocaine-associated stimuli, it may also occasion increase levels of cocaine self-administration. These findings support the hypothesis that the NMDA receptor can play a role in modulating the conditioned and primary reinforcing effects of cocaine.     

Clearing the Air: A Review of the Effects of Particulate Matter Air Pollution on Human Health

The World Health Organization estimates that particulate matter (PM) air pollution contributes to approximately 800,000 premature deaths each year, ranking it the 13th leading cause of mortality worldwide. However, many studies show that the relationship is deeper and far more complicated than originally thought. PM is a portion of air pollution that is made up of extremely small particles and liquid droplets containing acids, organic chemicals, metals, and soil or dust particles. PM is categorized by size and continues to be the fraction of air pollution that is most reliably associated with human disease. PM is thought to contribute to cardiovascular and cerebrovascular disease by the mechanisms of systemic inflammation, direct and indirect coagulation activation, and direct translocation into systemic circulation. The data demonstrating PM's effect on the cardiovascular system are strong. Populations subjected to long-term exposure to PM have a significantly higher cardiovascular incident and mortality rate. Short-term acute exposures subtly increase the rate of cardiovascular events within days of a pollution spike. The data are not as strong for PM's effects on cerebrovascular disease, though some data and similar mechanisms suggest a lesser result with smaller amplitude. Respiratory diseases are also exacerbated by exposure to PM. PM causes respiratory morbidity and mortality by creating oxidative stress and inflammation that leads to pulmonary anatomic and physiologic remodeling. The literature shows PM causes worsening respiratory symptoms, more frequent medication use, decreased lung function, recurrent health care utilization, and increased mortality. PM exposure has been shown to have a small but significant adverse effect on cardiovascular, respiratory, and to a lesser extent, cerebrovascular disease. These consistent results are shown by multiple studies with varying populations, protocols, and regions. The data demonstrate a dose-dependent relationship between PM and human disease, and that removal from a PM-rich environment decreases the prevalence of these diseases. While further study is needed to elucidate the effects of composition, chemistry, and the PM effect on susceptible populations, the preponderance of data shows that PM exposure causes a small but significant increase in human morbidity and mortality. Most sources agree on certain "common sense" recommendations, although there are lonely limited data to support them. Indoor PM exposure can be reduced by the usage of air conditioning and particulate filters, decreasing indoor combustion for heating and cooking, and smoking cessation. Susceptible populations, such as the elderly or asthmatics, may benefit from limiting their outdoor activity during peak traffic periods or poor air quality days. These simple changes may benefit individual patients in both short-term symptomatic control and long-term cardiovascular and respiratory complications.     

Aflatoxin exposures in the industrial setting: an epidemiological study of mortality

Mortality occurring between 1963 and 1980 in a small cohort (N = 71) of Dutch oil-press workers exposed between 1961 and 1969 to aflatoxins primarily via the respiratory route, was assessed and compared to that of a similar group of unexposed workers (N = 67). For the entire period of study, the observed mortalities for total-cancer and respiratory cancer were higher than expected in the aflatoxin-exposed group. Mortality observed in the comparison group was within the expected range. While two deaths in the exposed group were attributed to non-malignant liver disease, no primary liver tumours were observed. The greatest difference between observed and expected mortality was in the period between 1963 and 1968.     

Weekly docetaxel, zoledronic acid and estramustine in hormone-refractory prostate cancer (HRPC)

Summary Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m²) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53–83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1–8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens–Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen. Presented as a Poster at the XXth European Association of Urology Congress; 16–19 March 2005, Istanbul, Turkey.