Response to azacitidine in patients with chronic myelomonocytic leukemia according to overlap myelodysplastic/myeloproliferative neoplasms criteria.

BACKGROUND: Azacitidine (AZA) is approved for the treatment of high-risk chronic myelomonocytic leukemia (CMML) of myelodysplastic (MD) subtype. Data of response rates using the specific response criteria for this disease are scarce. The aim of this study was to evaluate the response to AZA in patients diagnosed with CMML from the Spanish Registry of Myelodysplastic Syndromes (MDS) applying the overlap myelodysplastic/myeloproliferative neoplasms (MDS/MPN) response criteria. METHODS: We retrospectively studied 91 patients with CMML treated with at least one cycle of AZA from the Spanish Registry of MDS. As it was a real-world study, the response rate was evaluated between cycle 4 and 6, applying the MDS/MPN response criteria FINDINGS: The overall response rate at cycle 4-6 was 58%. Almost half of the patients achieved transfusion independence and one quarter showed clinical benefit, regardless of the CMML French-American-British (FAB) and World Health Organization (WHO) subtypes and CMML Specific Prognosis Scoring (CPSS) risk groups. Toxicity was higher in the MD-CMML subtype. INTERPRETATION: In our series, most CMML patients achieved an overall response rate with AZA according to the overlap-MDS/MPN response criteria regardless of the CMML FAB and WHO subtypes and CPSS risk groups. Thus, AZA may also be a treatment option for patients with the myeloproliferative CMML subtype and those with a lower-risk CPSS, but symptomatic.

Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival.

BACKGROUND: Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. RESULTS: Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. CONCLUSIONS: Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival.

Evidence against a role for NLRP3-driven islet inflammation in db/db mice.

OBJECTIVES: Type 2 diabetes (T2D) is associated with chronic, low grade inflammation. Activation of the NLRP3 inflammasome and secretion of its target interleukin-1ß (IL-1ß) have been implicated in pancreatic ß cell failure in T2D. Specific targeting of the NLRP3 inflammasome to prevent pancreatic ß cell death could allow for selective T2D treatment without compromising all IL-1ß-associated immune responses. We hypothesized that treating a mouse model of T2D with MCC950, a compound that specifically inhibits NLRP3, would prevent pancreatic ß cell death, thereby preventing the onset of T2D. METHODS: Diabetic db/db mice were treated with MCC950 via drinking water for 8 weeks from 6 to 14 weeks of age, a period over which they developed pancreatic ß cell failure. We assessed metabolic parameters such as body composition, glucose tolerance, or insulin secretion over the course of the intervention. RESULTS: MCC950 was a potent inhibitor of NLRP3-induced IL-1ß in vitro and was detected at high levels in the plasma of treated db/db mice. Treatment of pre-diabetic db/db mice with MCC950, however, did not prevent pancreatic dysfunction and full onset of the T2D pathology. When examining the NLRP3 pathway in the pancreas of db/db mice, we could not detect an activation of this pathway nor increased levels of its target IL-1ß. CONCLUSIONS: NLRP3 driven-pancreatic IL-1ß inflammation does not play a key role in the pathogenesis of the db/db murine model of T2D.

Questions and controversies in innate immune research: what is the physiological role of NLRP3?

The NLRP3 inflammasome is a key component of the innate immune system that induces pro-inflammatory cytokine production and cell death. Although NLRP3 is activated by many pathogens, it only appears to be critical for host defense for a limited number of specific infections. NLRP3 is however strongly associated with the initiation and pathology of many inflammatory diseases. If NLRP3 function is largely redundant for host defense, but drives a number of inflammatory diseases, this raises the important question of why evolution has elected to maintain NLRP3 function. We propose that the primary physiological functions of NLRP3 in health are to engage pathways to clear noxious substances (e.g. protein aggregates and crystals), and to regulate metabolism. We discuss the newly identified functions for NLRP3 in metabolic homeostasis, and how NLRP3 beneficial functions in homeostasis may become detrimental during the onset of inflammatory and metabolic diseases. A common feature of most NLRP3-driven diseases is that they are associated with ageing or metabolic excess, and indeed, Nlrp3 deficiency promotes 'healthspan' in ageing mice. This suggests that beneficial functions of NLRP3 in youth may become increasingly countered by NLRP3-dependent pathology as an individual ages, and we propose a general model by which ageing or nutrient excess may provide a tipping point to switch NLRP3 function from beneficial to pathological. The physiological role of NLRP3 in healthy individuals remains incompletely understood and future research will need to address this if NLRP3 is to become a successful therapeutic target for the clinical management of inflammatory diseases.

[Consensus conference on providing information of adverse events to patients and relatives]. / Conferencia de consenso sobre información de eventos adversos a pacientes y familiares.

OBJECTIVE: To develop recommendations regarding «Information about adverse events to patients and their families¼, through the implementation of a consensus conference. MATERIAL AND METHODS: A literature review was conducted to identify all relevant articles, the major policies and international guidelines, and the specific legislation developed in some countries on this process. The literature review was the basis for responding to a series of questions posed in a public session. A group of experts presented the best available evidence, interacting with stakeholders. At the end of the session, an interdisciplinary and multi-professional jury established the final recommendations of the consensus conference. RESULTS: The main recommendations advocate the need to develop policies and institutional guidelines in our field, favouring the patient adverse events disclosure process. The recommendations emphasize the need for the training of professionals in communication skills and patient safety, as well as the development of strategies for supporting professionals who are involved in an adverse event. The assessment of the interest and impact of specific legislation that would help the implementation of these policies was also considered. CONCLUSIONS: A cultural change is needed at all levels, nuanced and adapted to the specific social and cultural aspects of our social and health spheres, and involves all stakeholders in the system to create a framework of trust and credibility in which the processing of information about adverse events may become effective.

Glucose control and outcome in patients with stable diabetes and previous coronary, cerebrovascular or peripheral artery disease. Findings from the FRENA Registry.

AIM: The aim of this study was to address the controversy over the influence of intensive glucose control on the risk for cardiovascular events in patients with Type 2 diabetes. METHODS: FRENA is an ongoing registry of stable outpatients with symptomatic coronary artery disease, cerebrovascular disease or peripheral artery disease. We compared the incidence of subsequent ischaemic events (myocardial infarction, stroke or critical limb ischaemia) in patients with Type 2 diabetes and mean HbA(1c) levels < 7.0% (< 53 mmol/mol) vs. those with HbA(1c) levels > 7.0% (> 53 mmol/mol). RESULTS: Of 974 patients with Type 2 diabetes, 480 (49%) had mean HbA(1c) levels < 7% (< 53 mmol/mol). Over a mean follow-up of 14 months, 126 patients (13%) had subsequent ischaemic events: myocardial infarction (43), stroke (29) and critical limb ischaemia (64). The incidence of subsequent ischaemic events was significantly lower in patients with mean HbA(1c) levels < 7.0% (< 53 mmol/mol) than in those with HbA(1c) levels > 7.0% (> 53 mmol/mol) (8.6 vs. 14 per 100 patient-years; rate ratio 0.6; 95% CI 0.4-0.9). These differences persisted after adjusting for potential confounders. However, this better outcome was only found in patients presenting with coronary artery disease (rate ratio 0.4; 95% CI 0.2-0.8), not in those with cerebrovascular disease (rate ratio 0.9; 95% CI 0.4-2.0) or peripheral artery disease (rate ratio 0.8; 95% CI 0.5-1.3). Patients with mean HbA(1c) levels < 7.0% (< 53 mmol/mol) also had a lower mortality (rate ratio 0.6; 95% CI 0.3-0.99). CONCLUSIONS: In secondary prevention, patients with diabetes and HbA(1c) levels < 7.0% (< 53 mmol/mol) had a lower incidence of subsequent ischaemic events and a lower mortality than those with HbA(1c) levels > 7.0% (> 53 mmol/mol). These differences appeared only in patients with coronary artery disease.

Long-term use of different doses of low-molecular-weight heparin versus vitamin K antagonists in the treatment of venous thromboembolism.

BACKGROUND: We evaluated whether the incidence of recurrent venous thromboembolic events (VTEs) during and after therapy differs for patients treated with full or reduced doses of low-molecular-weight heparin (LMWH) used long term compared with vitamin K antagonists (VKAs). METHODS: We identified randomized studies of long-term treatment with LMWH or VKA by searching MEDLINE, EMBASE, BIOSIS, and PASCAL. Seventeen studies were included, with 4,002 patients. RESULTS: In the assessment at 12 months of 1,957 patients without cancer, the recurrence rates of VTE in the LMWH/VKA groups were 8.3%/7.6% in the studies using full doses and 12.3%/12.1% in those using prophylactic doses. However, combined analysis after treatment to 1 year showed a nonsignificant (NS) trend to lower recurrent symptomatic VTE in favor of VKA (RR = 1.46, 95% CI 0.96-2.23). In 1,292 patients with cancer the recurrence rates of VTE in the LMWH/VKA groups were 6.5%/17.9% (p = 0.005) in the studies using full doses, 7.1%/13.4% (p = 0.002) in the studies using intermediate doses, and 14.3%/19.1% (p = NS) in the studies using prophylactic doses. Furthermore, the recurrences of VTE after discontinuation of treatment in the LMWH/VKA groups were 1.6%/9.5% (RR = 0.25, 95% CI 0.06-1.1) in 252 patients with full doses and 12%/7.4% (RR = 1.49, 95% CI 0.3-7.48) in 52 patients with prophylactic doses. In this population with cancer, the full-treatment LMWH regimen did not produce more major bleeding events than intermediate or prophylactic doses (5.1% vs. 6.3% or 8.1%, respectively). CONCLUSION: Full-dose LMWH for 3-6 months is as safe as intermediate and prophylactic doses for the long-term treatment of deep vein thrombosis. In patients with cancer it appears that there is an excess of VTE recurrence after treatment with prophylactic doses that does not occur with full therapeutic doses.

Differences in cardiovascular mortality in smokers, past-smokers and non-smokers: findings from the FRENA registry.

BACKGROUND: The influence of smoking on outcome in patients with coronary artery disease (CAD) is controversial. Even less is known about its influence in patients with cerebrovascular (CVD), or peripheral artery (PAD) disease. PATIENTS AND METHODS: FRENA is an ongoing, observational registry of consecutive outpatients with symptomatic CAD, CVD, or PAD. We reviewed their cardiovascular mortality according to smoking status. RESULTS: As of May 2008, 2501 patients had been enrolled in FRENA. Of these, 439 (18%) were current smokers, 1086 (43%) past-smokers, 976 (39%) had never smoked. Current- and past-smokers were 10 years younger, more often males, and more likely to have chronic lung disease, but had diabetes, hypertension, heart failure, or renal insufficiency less often than non-smokers. Over a mean follow-up of 14 months, 123 patients died (cardiovascular death, 68). On univariate analysis, current smokers had a significantly lower rate of cardiovascular death: 1.1 (95% CI: 0.4-2.4) per 100 patient-years in current smokers; 1.9 (95% CI: 1.2-2.8) in past-smokers; 3.5 (95% CI: 2.5-4.7) in non-smokers, with no differences between patients with CAD, CVD or PAD. Mean age at cardiovascular death was 82+/-6.4; 70+/-9.9 and 67+/-15 years, respectively. On multivariate analysis, smoking status was not independently associated with a lower risk for cardiovascular death. CONCLUSIONS: Current and past-smokers with CAD, CVD or PAD had a less than half cardiovascular mortality than those who never smoked, but this may be explained by the confounding effect of additional variables. They died over 10 years younger than non-smokers.

Arterial mapping with Duplex ultrasound: diagnostic-therapeutic strategy in patients with critical lower-limb ischemia.

AIM: Arteriography is the gold-standard in decision making in patients with critical lower-limb ischemia. Such method is not bereft of side effects and only gives morphologic information about lesions. Duplex allows to evaluate hemodynamically the arteriosclerotic lesions of ischemic lower limbs non-invasivelly and with the same reliability, in some studies, as angiography. Aim of this study was to determine the value and safety of arterial ultrasonic mapping in decision making for treatment of critical lower-limb ischemia. METHODS: This was a prospective and comparative study in patients with critical lower-limb ischemia recruited from March 2005 to June 2006. Ultrasonic arterial mapping was performed in 130 patients. Arteriography was performed only in those patients with elevated risk of major amputation or if ultrasound was not feasible (44 patients). Patients were randomized into two groups according to decision making criteria: 1) group A based on mapping alone; 2) group B based on arteriography. There was no statistical difference between risk factors in the two groups (P>0.05). Cumulative patency was recorded and compared at one and three months (Log Rank) as well as degree of concordance of decision making using mapping and arteriography in the group with both tests (B); and degree of concordance of the two tests with decision making based on intraoperative findings. RESULTS: The degree of concordance between mapping and arteriography was 84.1% (P<0.0001), and the degree of concordance between mapping and arteriography with respect to final decision according to intraoperative findings was 93.1% and 97.7%, respectively (P<0.0001). There were no statistically significative differences in patency rates at one and three months between the two groups (P>0.05). CONCLUSIONS: Ultrasonic arterial mapping is sufficient and comparable to arteriography for purposes of decision making in patients with critical lower-limb ischemia.

A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis.

OBJECTIVE: To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT). DESIGN: A randomised, open-label trial. MATERIAL AND METHODS: In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months. RESULTS: During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group. CONCLUSIONS: Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer.

The importance of a standing position in the diagnosis of Nutcracker phenomenon by duplex sonography.

AIM: To determine the clinical usefulness of Doppler ultrasonography in the diagnosis of the Nutcracker phenomenon, as an alternative to computed tomographic scans (CT). METHODS: This study consisted of 52 patients that presented with intermittent hematuria of unknown origin between January 2006 to April 2008. Doppler ultrasonography was used to assess the left renal vein (LRV) by measuring the anteroposterior (AP) diameter and peak systolic velocity (PSV) in supine and standing positions, at the hilar and interaortomesenteric portions of the LRV. These data were compared with CT scans. The sensitivity and specificity of duplex sonography was determined using the AP diameter and PSV ratios to assess the cut-off levels. Kappa (k) statistic was also evaluated. RESULTS: mean AP diameters of the LRV measured by Doppler sonography were 8.38 mm at the hilar and 3.17 mm under the SMA, compared to 9.3 mm (hilar) and 3.2 mm (SMA) in the supine and standing position respectively. The PSV in the supine position was 25.77 cm/s and 115.48 cm/s, respectively, compared to 25.54 cm/s and 125.96 cm/s in the standing position. The cut-off levels were 3.85 (sensitivity: 61.5%, specificity: 80.8%, k:0.42) for the supine and 4.12 (sensitivity:61.5%, specificity: 65.4%, k: 0.27) for the standing AP diameter, 2.99 (sensitivity: 92.3%, specificity: 73.1%, k: 0.65) for the supine and 3.73 (sensitivity: 96.4%, specificity: 79.2%, k: 0.76) for the standing PSV. CONCLUSIONS: Our data show that the standing PSV ratio is the best parameter for to detecting entrapment of the LRV.

Early mobilisation in patients with acute deep vein thrombosis does not increase the risk of a symptomatic pulmonary embolism.

AIM: The purpose of the study was to determine if early mobilisation in patients with acute lower limb deep vein thrombosis (DVT) increases the incidence of symptomatic pulmonary embolism (PE) and to evaluate the predisposing factors for PE such as location of the thrombus and duration of symptoms. METHODS: The current study was a prospective randomised clinical trial. Between January 2005 and December 2007, 219 patients with acute lower limb DVT were enrolled in the study (118 males and 101 females); the mean age was 64.2 years. INCLUSION CRITERIA: <15 days of initial symptoms, life expectancy >1 year, no life-threatening clinical conditions, and signed informed consent. The patients were randomised into two groups. Group A, 105 patients (47.9%) were hospitalized and received 5 days of bed rest; Group B, 114 patients (52.1%) received care at home with early walking and compression stockings. The primary end point was the presence of symptomatic PE during the first 10 days of treatment. The relationships between the duration of symptoms, location of the thrombus, and symptomatic PE were also analysed. RESULTS: Five cases of symptomatic PE were detected (2.3%), three in Group B and two in Group A. There was no significant difference in the occurrence of new PE between the two groups (P=0.54). Likewise, no difference was detected based on the duration of symptoms (P=0.62) and the location of the thrombus (P=0.43). CONCLUSIONS: In acute DVT , early walking, thrombus location, and duration of the symptoms did not influence the incidence of symptomatic PE.

Effect of dehydroleucodine on histamine and serotonin release from mast cells in the isolated mouse jejunum.

OBJECTIVE AND DESIGN: DhL, a lactone isolated from Artemisia douglasiana, prevents gastrointestinal damage elicited by necrosis-inducing agents and exhibits antiinflammatory action. This work examines the effect of DhL on compound 48/80-induced histamine and serotonin release in the isolated mouse jejunum, to determine whether DhL inhibits mediator release from mast cells at the enteric level. MATERIAL: Thirty jejuna from male Balb-c mice were used for the studies. TREATMENT: Samples were incubated sequentially in 9 test tubes containing RBS or 10 microg/ml compound 48/80 or 1.6 mmol/l + 10 microg/ml compound 48/80 at 37 degrees C for 90 minutes (10 min per tube). METHODS: Histamine and serotonin release studies, quantification of granulated mast cells, and evaluation of mast cell ultrastructure were carried out. Differences between groups were determined using analysis of variance followed by Tukey-Kramer multiple comparisons test. RESULTS: Compound 48/80 increased histamine and serotonin release by the tissue (141.95 +/- 62.58 pg/mg tissue vs basal 5.45 +/- 1.04, P<0.01 and 20.04 +/- 2.81 vs basal 9.24 +/- 1.56 ng/ mg tissue, P<0.01, respectively), decreased the number of granulated submucosal mast cells (0.077 +/- 0.0035 vs basal 0.14 +/- 0.015, P<0.05), and elicited evident granule ultrastructural changes. These effects were reduced by dehydroleucodine (19.51 +/- 7.88, P<0.01; 12.69 +/- 1, P<0.05 and 0.143 +/- 0.014, P<0.05, respectively). CONCLUSION: The lactone inhibits compound 48/80-induced histamine and serotonin release from mast cells in the isolated mouse jejunum.

Effect of creatine on performance of militarily relevant tasks and soldier health.

PURPOSE: Determine the short-term effects of creatine supplementation on performance of military tasks, thermoregulation, and health risks. METHODS: Male military personnel were randomly assigned to a creatine (CR; N = 8) or a placebo (CON; N = 8) supplementation group. Testing was conducted at baseline, after a 6-day load phase (20 g/d), and after 4 weeks of taking 6 g/d. Measurements included body composition, liver/kidney function tests, core body temperatures during a 10-mile march and 5-mile run, and performance on physical tasks. RESULTS: Serum and urine creatine increased significantly in the CR group. Body mass and number of pull-ups performed increased significantly in the CR group but not the CON group by week 4. No significant differences between the CR and CON groups were found for other performance measures, body composition, core body temperature, or other biochemical measures. CONCLUSION: Creatine supplementation increased body mass and pull-up performance but did not cause acute health problems. Creatine did not increase core temperature compared with placebo under the environmental conditions of the study, and it is unlikely that creatine will enhance the overall readiness or performance of soldiers.

Antibacterial activities and pharmacokinetics of E-4767 and E-5065, two new 8-chlorofluoroquinolones with a 7-azetidin ring substituent.

E-4767 [(-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-8-chloro-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid] and E-5065 [(-)-7-(3-amino-1-azetidinyl)-8-chloro-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid] are two new chlorofluoroquinolones with an azetidine moiety at position 7. Their in vitro activities were evaluated in comparison with those of ciprofloxacin, ofloxacin, fleroxacin, and tosufloxacin, while ciprofloxacin was used as a reference for in vivo studies. Against gram-positive organisms, E-4767 and E-5065 were, in general, eight- and fourfold more active than tosufloxacin, which is the most potent of the reference compounds. E-4767 and E-5065 were also more potent than the reference compounds against all species of enteric bacteria tested. The MICs of E-4767 and E-5065 at which 90% of the isolates tested were inhibited (MIC(90)s) were 0.007 to 0.5 microg/ml and 0.03 to 2 microg/ml, respectively, for gram-positive organisms and

Support for the progressively finer attributes theory: two experiments.

In this paper two experiments support and amplify Coll and Coll's 1994 Progressively Finer Attributes Theory of Memory Trace Development. Important to the current paper are five propositions of this theory. (1) The memory trace develops along an attribute dimension from coarse/general to fine/specific attributes. (2) Forgetting is a reverse movement from fine to coarse as increasingly less fine attributes are lost. (3) A memory trace consists of a bundle of defining attributes and relating' attributes. There are no constraints on the type of attribute included in the attribute bundle or in the order of types acquired. The trace name is defined by the attribute bundle it represents. (4) Access to any defining attribute of a memory trace gives full access to all other attributes of the trace bundle. (5) In the early phases of trace development the attributes are preeminent in recall but, as familiarity with a to-be-learned item increases, the attributes become increasingly cohesive and the name assumes preeminence. As forgetting progresses, there is a return to the original state (attributes are preeminent). Exp. 1 supports Propositions 3 and 4 and Exp. 2 supports Propositions 3 and 5. Both experiments provide validation of Propositions 1 and 2 beyond that in prior work. The authors present arguments that the coarse-to-fine movement of the Progressively Finer Attributes Theory is the mechanism by which Levels of Processing operates.

Effectiveness and safety of prehospital urapidil for hypertensive emergencies.

The objective was to evaluate both the effectiveness and safety of urapidil in management of hypertensive emergencies (HE) in the prehospital setting. This was an open, prospective study for 6 months. We evaluated systolic (SBP), diastolic (DBP), and mean blood pressure (MBP), and heart rate (HR) with continuous noninvasive hemodynamic monitoring in 16 consecutive cases of HE. We used urapidil at different doses (25 to 100 mg) at 5 minute intervals, according to the blood pressure response. The basal DBP was 127 +/- 16 mmHg. Urapidil was effective in 15 patients. ANOVA test showed a significant drop out in DBP (P <.0001) and HR (P <.004). The highest decrease was obtained in the first 10 minutes. The decrease in DBP and HR values were significant at 5 minutes versus basal (P <.05) and at 10 versus 5 minutes (P <.01). All adverse effects had little relevance. Urapidil is effective and safe in management of HE when used by a medical team in the prehospital setting.