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The proton exchange membrane fuel cells (PEMFC) have been developed mainly as a power source for vehicles, power generation and consumer electronics since they combine high energy conversion efficiency at relatively low temperatures without pollutants emission in the environment. An electrode for a PEMFC is a layered structure composed by a catalyst layer deposited on a porous carbon substrate. The substrate is usually covered by a diffusion layer that enhances the gas and water flow. Platinum nanoparticles supported by carbon microparticles are commonly employed as catalyst layer. In this work an extreme ultra-low loading of Pt catalyst (< 0.02 mg/cm2) has been deposited by magnetron sputtering on gas diffusion electrodes, with different carbon supports (Vulcan and SuperP), in order to enhance the activity of PEM fuel cells. The morphology (shape and grain size) and microstructure have been studied combining field emission scanning electron microscopy (FEG-SEM), grazing incidence synchrotron x-ray diffraction (GIXRD) and x-ray photoelectron spectroscopy (XPS). The results presented here concern the evolution of the cluster size and shape after the ageing, induced by cyclic voltammetry for methanol oxidation reaction.

Extensive efforts are focused on the development of Direct Methanol Fuel Cells, due to the intrinsic advantages of this type of devices for mobile power supply system. One of the major drawback of the DMFC resides in the easy poisoning of the anode electrocatalyst (platinum) by COlike reaction intermediates, which implies the need of high platinum load in order to obtain reasonable performances. The development of platinum alloys is considered one of the promising routes for overcoming this problem: the second metal in fact acts as inhibitor of the Pt poisoning. In this work we have combined the use of unconventional methods to deposit the electrocatalyst nanoparticles with unconventional carbon supports. PtAu alloys have been deposited by sputter deposition process on carbon nanofibers with platelet morphology grown by plasma enhanced chemical vapour deposition on carbon paper. Cyclic voltammetry in H2SO4 was used to determine the electrochemical active surface and the electrocatalytic performance for methanol oxidation reaction. Even at lower Pt load, respect to the ones prepared with commercial catalysts supported on carbon black, the innovative electrodes showed higher performance and stability.

A calibration procedure for the detection efficiency of energy dispersive X-ray spectrometers (EDS) used in combination with scanning electron microscopy (SEM) for standardless electron probe microanalysis (EPMA) is presented. The procedure is based on the comparison of X-ray spectra from a reference material (RM) measured with the EDS to be calibrated and a reference EDS. The RM is certified by the line intensities in the X-ray spectrum recorded with a reference EDS and by its composition. The calibration of the reference EDS is performed using synchrotron radiation at the radiometry laboratory of the Physikalisch-Technische Bundesanstalt. Measurement of RM spectra and comparison of the specified line intensities enables a rapid efficiency calibration on most SEMs. The article reports on studies to prepare such a RM and on EDS calibration and proposes a methodology that could be implemented in current spectrometer software to enable the calibration with a minimum of operator assistance.

We present the first protocol that reaches asynchronous Byzantine consensus in two communication steps in the common case. We prove that our protocol is optimal in terms of both number of communication steps and number of processes for two-step consensus. The protocol can be used to build a replicated state machine that requires only three communication steps per request in the common case. Further, we show a parameterized version of the protocol that is safe despite f Byzantine failures and, in the common case, guarantees two-step execution despite some number t of failures (t /spl les/ f). We show that this parameterized two-step consensus protocol is also optimal in terms of both number of communication steps and number of processes.

This paper describes a general approach to constructing cooperative services that span multiple administrative domains. In such environments, protocols must tolerate both Byzantine behaviors when broken, misconfigured, or malicious nodes arbitrarily deviate from their specification and rational behaviors when selfish nodes deviate from their specification to increase their local benefit. The paper makes three contributions: (1) It introduces the BAR (Byzantine, Altruistic, Rational) model as a foundation for reasoning about cooperative services; (2) It proposes a general three-level architecture to reduce the complexity of building services under the BAR model; and (3) It describes an implementation of BAR-B the first cooperative backup service to tolerate both Byzantine users and an unbounded number of rational users. At the core of BAR-B is an asynchronous replicated state machine that provides the customary safety and liveness guarantees despite nodes exhibiting both Byzantine and rational behaviors. Our prototype provides acceptable performance for our application: our BAR-tolerant state machine executes 15 requests per second, and our BAR-B backup service can back up 100MB of data in under 4 minutes.

Abstract We have developed a new quantitative native PAGE mobility shift assay, which allows for the measurement of binding affinities for interacting protein pairs, one of which is fluorescently labelled. We have used it to examine recognition of the Simian virus 40 (SV40) large tumour T-antigen (T-ag) nuclear localisation sequence (NLS) by members of the importin (Imp) superfamily of nuclear transport proteins. We demonstrate that the T-ag NLS binds to the Imp α/β heterodimer in NLS-dependent manner, determining that it binds with eight-fold higher affinity (340 nM), when compared to Imp α alone, consistent with autoinhibition of Imp αwhen not complexed with Imp β. The mobility shift assay is able to detect nM binding affinities, making it a sensitive and useful tool to analyse protein–protein interactions in solution.

We describe a new architecture for Byzantine fault tolerant state machine replication that separates agreement that orders requests from execution that processes requests. This separation yields two fundamental and practically significant advantages over previous architectures. First, it reduces replication costs because the new architecture can tolerate faults in up to half of the state machine replicas that execute requests. Previous systems can tolerate faults in at most a third of the combined agreement/state machine replicas. Second, separating agreement from execution allows a general privacy firewall architecture to protect confidentiality through replication. In contrast, replication in previous systems hurts confidentiality because exploiting the weakest replica can be sufficient to compromise the system. We have constructed a prototype and evaluated it running both microbenchmarks and an NFS server. Overall, we find that the architecture adds modest latencies to unreplicated systems and that its performance is competitive with existing Byzantine fault tolerant systems.

Wide-area systems are gaining in popularity as an infrastructure for running scientific applications. From a fault tolerance perspective, these environments are challenging because of their scale and their variability. Causal message logging protocols have attractive properties that make them suitable for these environments. They spread fault tolerance information around in the system providing high availability. This information can also be used to replicate objects that are otherwise inaccessible because of network partitions. However, current causal message logging protocols do not scale to thousands or millions of processes. We describe the Hierarchical Causal Message Logging Protocol (HCML) that uses a hierarchy of shared logging sites, or proxies, to significantly reduce the space requirements as compared with existing protocols. These proxies also act as caches for fault tolerance information and reduce the overall message overhead by as much as 50%. HCML also leverages differences in bandwidth between processes that reduces overall message latency by as much as 97%. Copyright © 2003 John Wiley & Sons, Ltd.

Background: This prospective study examined the appropriate use of EGD in an open-access system with the American Society for Gastrointestinal Endoscopy (ASGE) guidelines and determined whether the ASGE guidelines were associated with relevant endoscopic findings. Methods: In a cohort of 1777 consecutive patients referred for open-access EGD, the proportion of patients who underwent EGD for appropriate indications was prospectively assessed. The relationship between appropriateness and the presence of clinically relevant endoscopic diagnoses was assessed by calculating (1) the likelihood ratio, positive and negative, of the indications; and (2) the change in the probability of relevant endoscopic diagnoses in the presence of the ASGE criteria. Results: The rate for EGDs ''generally not indicated'' was 15.6%. Relevant endoscopic diagnoses were present in 47.4% of cases with ASGE indications versus 28.8% of patients without appropriate indications as defined by the ASGE criteria (OR: 2.23; 99% CI [1.55, 3.22]; p < 0.01). A similar difference was observed for erosive gastritis (OR: 1.86; 99% CI [1.17, 2.95]; p < 0.01), erosive esophagitis (OR: 1.48; 99% CI [0.87, 2.52]; p < 0.05), and Barrett's esophagus (OR: 9.76; 99% CI [0.72, 132]; p < 0.05). The pretest probability of finding a relevant endoscopic diagnosis was modified slightly when an ASGE indication(s) was present and decreased markedly when ASGE criteria were absent. Conclusions: The use of the ASGE guideline for appropriate indications for EGD can improve patient selection for the procedure. However, to avoid missed diagnoses of serious disease, use of the guidelines must be tailored to the specific clinical setting. (Gastrointest Endosc 2002;56:714-9.)

High-reflectivity dense multilayer coatings were produced for the ultraviolet spectral region. Thin-film single layers and UV mirrors were deposited by ion plating and plasma ion-assisted deposition high- energetic technologies. Optical characterizations of HfO_2 and SiO_2 single layers are made. The optical constants obtained for these two materials are presented. HfO_2 and SiO_2 mirrors with a reflectance of ∼99% near 250 nm are reported.

Working with wavelengths shorter than the deep ultraviolet involves the development of dedicated optics for free-electron lasers with devoted coating techniques and characterizations. High-performance deep-ultraviolet optics are specially developed to create low-loss, high-reflectivity dielectric mirrors with long lifetimes in harsh synchrotron radiation environments. In February 2001, lasing at 189.7 nm, the shortest wavelength obtained so far with free-electron-laser oscillators, was obtained at the European Free-electron-laser project at ELETTRA Synchrotron Light Laboratory, Trieste, Italy. In July 2001, 330-mW extracted power at 250 nm was measured with optimized transmission mirrors. Research and development of coatings correlated to lasing performance are reported.

Abstract.: Casual message-logging protocols have several attractive properties: they introduce no blocking, send no additional messages over those sent by the application, and never create orphans. Causal message logging, however, does require the casual effects of the deliveries of messages to be tracked. The information concerning causality tracking is piggybacked on application messages, and the amount of such information can become large. In this paper we study the cost of tracking causality in causal message-logging protocols. One can track causality as accurately as possible, but to do so requires piggybacking a considerable amount of additional information. One can reduce the amount of piggybacked information on each message by reducing the accuracy of causality tracking. But then, causal message logging may piggyback the reduced amount of information on more messages. We specify six different methods of tracking causality, each representing a natural choice based on the specification of causal message logging. We describe how these six methods can be implemented and compare them in terms of how large of a piggyback load they impose. This load depends on the application that is using causal message logging. We characterize some applications for which a given method has the smallest piggyback load, and study using simulation the size of the piggyback load for two different models of applications.

Twenty eight short sediment cores, collected along six transects in two areas influenced by the frontal system formed by the Po River, were analysed for Th and Cs in order to improve our knowledge on short time scale sediment deposition, accumulation and mixing. Sedimentological and mineralogical parameters were also analysed._ The decreasing Cs activities and C/N values in surface sediments indicate a decreasing input of terrestrial material during the study period. Furthermore, low excess thorium activities and inventories at some sites, together with low sedimentary organic matter concentrations in the southern area, suggest that the productivity in summer 1997 was lower than in 1996. Temporal and spatial shifts of the front exert a strong influence on short time scale deposition of particulate matter in the northern area, while the front position is more stable in the southern area, influencing both seasonal and interannual deposition._ The comparison between apparent seasonal and pluri-annual accumulation rates suggests, for the northern area, a sedimentation pattern characterized by temporal deposition of material on to the sea floor, with periodical resuspension. The net apparent accumulation is 0.1-0.4 r g r cm r yr. The same occurs for the southern area, where values are higher, probably due to the longer persistence of the frontal system in the same area over the years. Here, both seasonal and pluri-annual deposition showed the same pattern, but seasonal values were two to three times higher with a net apparent accumulation rate of 0.3-0.8 r g r cm r yr. Organic carbon and nitrogen concentrations are generally less than 1.3 and 0.2% d.w., with lower values in the southern area. By contrast, mass fluxes showed higher values in the southern area, while the rate of removal over a pluri-annual time scale is generally high.

Aims of this study were to evaluate: (1) whether upper gastrointestinal endoscopy (UGE) is used appropriately according to the American Society for Gastrointestinal Endoscopy (ASGE) and British Society of Gastroenterology (BSG) guidelines in a hospital setting and (2) whether there is any relationship between appropriateness of UGE and the presence of lesions detected by endoscopy. %Indications and endoscopic findings for 734 consecutive UGE performed in 697 inpatients were retrospectively evaluated using ASGE and BSG guidelines to determine appropriateness of referrals. UGE showing endoscopic findings that had direct therapeutic or prognostic consequences were classified as “positive”; the other UGEs were classified as “negative.” In all, 46% of UGEs were “positive,” 54% “negative,” and 61.7% and 23.2% of UGEs were inappropriate according to ASGE and BSG guidelines, respectively (P< 0.001). The probability of finding a positive endoscopy was significantly higher in UGE rated as appropriate than in those rated as inappropriate on the basis of ASGE guidelines (P< 0.001), but not on the basis of BSG guidelines. Endoscopies rated as inappropriate according to ASGE and BSG criteria showed a positive finding in 37.3% and 42.3% of cases, respectively (not significant difference). Multivariate analysis showed that the positive finding is directly related to age (P< 0.05), male gender (P< 0.001), prior UGE (P< 0.05), hematemesis (P< 0.001), and inversely related with upper abdominal pain (P< 0.01) and dyspepsia (P< 0.05). In hospitalized patients, UGE is frequently used for inappropriate indications, according to both ASGE and BSG guidelines. However, the actual clinical usefulness of appropriateness criteria, such as those proposed by ASGE and BSG, is questionable, as their strict observance could lead to missing a large number of significant endoscopic findings.

High-crystalline CdS nanocrystals, prepared by means of an improved synthetic route that exploits a quaternary water-in-oil microemulsion are immobilized on gold and quartz substrates by self-assembly. The obtained nanocrystals and layers are characterised by scanning tunneling microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and UV–vis spectroscopy. The results indicate that the CdS nanocrystals show a good adherence to the substrate, are quite stable in air for months, and still retain their size and quantum properties after immobilization. The data are discussed in terms of the increased stability of the nanocrystals in solution due to the presence of the co-surfactant that acts as capping agent.

Purpose: The purpose of this article was to investigate the relationship between analgesia, sedation, and memory of intensive care. Patients and Methods: One hundred fifty-two adult, cooperative intensive care unit (ICU) patients were interviewed 6 months after hospital discharge about their memory of intensive care. The patient was considered to be cooperative when he/she was aware of self and environment at the interview. The patients were grouped as follows: A (45 patients) substantially no sedation, B (85) morphine, and C (22) morphine and other sedatives. Results: The patients having no memory of intensive care were 38%, 34%, and 23% respectively, in the three groups. They were less ill, according to SAPS II (P < .05), and had a shorter ICU stay (P < .01). Group C patients were more seriously ill according to SAPS II, duration of mechanical ventilation, and length of stay in ICU and in hospital (P < .001). The incidence of factual, sensation, and emotional memories was not different among the three groups. Females reported at least one emotional memory more frequently than males (odds ratio 4.17; 95% CI 10.97-1.59). Conclusions: The patients receiving sedatives in the ICU are not comparable with those receiving only opiates or nothing, due to the different clinical condition. The lack of memory of intensive care is present in one third of patients and is influenced more by length of stay in ICU than by the sedation received. Sedation does not influence the incidence of factual, sensation, and emotional memories of ICU admitted patients. Females have higher incidences of emotional memories than males. Copyright (C) 2001 by W.B. Saunders Company

Different national attitudes exist between countries in Europe concerning eradication of Helicobacter pyloriinfection due to the wide differences in Helicobacter pyloriprevalence, gastric cancer risk, bacterial resistance to antibiotics, health care systems and financial resources. The Cervia Working Group Report has been established in order to fill the gap in the absence of National Guidelines in Italy concerning the diagnosis and treatment of Helicobacter pyloriinfection. The recommendations made are, by and large, similar to the European Guidelines but differ slightly with regard to the “test-and-treat” approach to young dyspeptics without sinister symptoms. In the absence of a national validation of this strategy a case-by-case assessment of dyspepsia has been promoted, both at primary care and specialist level. Another area of partial disagreement concerns the eradication of Helicobacter pyloriin patients undergoing long-term proton pump inhibitor treatment which has not been generally recommended as scientific evidence in support of this policy is at present rather weak.

We propose to exploit multivalent binding of solid-binding peptides (SBPs) for the physical attachment of antifouling polypeptide brushes on solid surfaces. Using a silica-binding peptide as a model SBP, we find that both tandem-repeated SBPs and SBPs repeated in branched architectures implemented via a multimerization domain work very well to improve the binding strength of polypeptide brushes, as compared to earlier designs with a single SBP. At the same time, for many of the designed sequences, either the solubility or the yield of recombinant production is low. For a single design, with the domain structure B-M-E, both solubility and yield of recombinant production were high. In this design, Bis a silica-binding peptide, Mis a highly thermostable, de novo-designed trimerization domain, and Eis a hydrophilic elastin-like polypeptide. We show that the B-M-Etriblock polypeptide rapidly assembles into highly stable polypeptide brushes on silica surfaces, with excellent antifouling properties against high concentrations of serum albumin. Given that SBPs attaching to a wide range of materials have been identified, the B-M-Etriblock design provides a template for the development of polypeptides for coating many other materials such as metals or plastics.

SiO_2 thin films (≈100 nm thick) with transmittivity and a laser damage threshold nearly equal to those of bulk material are deposited on silica substrates by the technique of ion-assisted electron-beam evaporation. The influence of film packing density on the laser damage threshold is investigated by the technique of photoacoustic probe beam deflection. It is shown that films with lower packing density may have a higher laser damage threshold and as a consequence better heat dissipation.

Summary Helicobacter pylori colonization and the incidence, severity, activity and topography of gastritis were investigated systematically in antrum and corpus mucosal biopsies of 1177 subjects undergoing endoscopy in the absence of gastric complaints (asymptomatic, 49) or for non-ulcer dyspepsia (NUD; 631 patients, 72 of whom had gastric and/or duodenal erosions), active gastric ulcer (GU, 76 patients), active duodenal ulcer (DU, 138 patients), and healed gastric (HGU, 39 cases) or duodenal ulcer (HDU, 230 cases). In the antrum,H. pylori colonization and the incidence, severity and activity of gastritis increased progressively in the sequence asymptomatic, erosion-free NUD, erosive NUD, healed ulcer and active ulcer. The same trend was observed in the corpus as regardsH. pylori and gastritis incidence, whereas the severity and activity of gastritis were lower in active DU and erosive NUD and higher in active, proximal GU than in the remaining patients. Active DU and erosive NUD showed the highest incidence of nonatrophic gastritis and lowest type-A or AB atrophic gastritis, while active GU had lowest normal mucosa or type-A gastritis and highest type-B atrophic gastritis. In conclusion,H. pylori colonization and gastritis incidence, severity and, especially, activity of the antrum might all contribute to mucosal erosion and ulceration, whereas the same factors, at least in part and with the exception of proximal GU, seem to have a preventive role when affecting corpus mucosa.

We have measured serum immunoreactive pancreatic elastase 1 concentrations in 90 patients with pancreatic cancer in order to determine its usefulness in the diagnosis of this tumor. Abnormal elastase 1 concentrations were found in only 58 (64.4) of the 90 patients. Fifty (55.5) had abnormally high values, and eight (8.9) had abnormally low values. No significant differences in elastase 1 levels were observed between patients with resectable cancer (n = 15) and those with unresectable cancer (n = 75). Moreover, no significant differences were found between elastase 1 concentrations of patients with pancreatic cancer and those of 71 patients with chronic pancreatitis. We conclude that serum elastase 1 measurement does not represent a significant advance in the diagnosis, whether early or late, of pancreatic cancer.

Exocrine pancreatic function was studied in 15 patients with hypothyroidism and 15 healthy subjects by means of the amino acid consumption test, a new tubeless test based on the measurement of plasma amino acid uptake by the pancreas during pancreatic enzyme synthesis stimulation. Nine of the 15 patients were also studied after they had become euthyroid following thyroxine treatment. Pancreatic function was significantly reduced in patients with hypothyroidism compared with healthy subjects. Treatment with thyroxine restored pancreatic function to normal. In two additional hypothyroid patients studied by means of duodenal intubation, pancreatic secretion of both bicarbonate and enzymes was found to be significantly decreased. It was concluded that the thyroid gland plays an essential role in maintaining the functional integrity of the exocrine pancreas in humans.

A total of 615 healthy fertile women (518 pill users and 97 non-users) were examined by real-time ultrasonography for fasting gallbladder volume, gallstones and biliary dysmorphism. None of the six examined combinations of oral contraceptives appeared to influence fasting gallbladder volume significantly. When fasting gallbladder volumes were reanalyzed according to the presence or absence of recognized biliary riskfactors, significant modifications were detected, in both pill users and non-users. These changes related only to age and parity. Relative risks of cholelithiasis and biliary dysmorphism were not affected by contraceptive treatment.

In Kalotermes flavicollis Fabr. (Isoptera, Kalotermitidae) the tryptophan metabolites were determined by paper chromatography.The metabolites, present in varying amounts in all the castes and stages studied, seem to be synthetized by Kalotermes flavicollis itself and not by symbionts in the insect intestine.The differences in the quantities of the metabolites among the groups do not seem to be correlated with the castes and stages.The results are discussed in relation to the synthesis of ommochromes.

Background: In a significant number of patients affected by the irritable bowel syndrome, an adverse reaction to food is proposed to be a causative factor. A diet that eliminates the offending foods is the obvious treatment for such adverse reactions. Compliance with a dietetic regimen is often poor and sometimes not completely free from risks. Methods: Since the diarrheic type of irritable bowel syndrome seems mainly affected by food intolerance, and previous observations suggested that oral cromolyn sodium is effective in such patients, a multicenter therapeutic trial in the diarrheic type of irritable bowel syndrome was carried out in 346 of 409 patients with this disease, to evaluate the effects of oral cromolyn sodium and compare its efficacy with that of an elimination diet. Results: Symptoms related to the irritable bowel syndrome improved in 60% of patients treated with elimination diet and in 67% of those treated with oral cromolyn sodium (1500 mg/day) for 1 month. Moreover, in both groups clinical results were significantly better in the patients positive to the skin prick test than in the negative ones. Conclusions: These results confirm the high prevalence of adverse reactions to foods in diarrheic irritable bowel syndrome and the usefulness of cromolyn sodium treatment in these patients.

The methylation of the human oestrogen receptor (ER) gene was analysed by restriction enzymes in normal and neoplastic human breast tissues and cell lines. CCGG sequences in regions inside the gene, which are methylated both in normal breast and in tissues that are not the target of the oestrogen, are hypomethylated in 30% of tumours, both ER+ and ER- carcinomas. Moreover, 5' sequences of the gene, which are hypomethylated in normal breast and not in tissues not the target of oestrogen, are methylated to a lower degree in ER+ carcinomas, whereas they are methylated to a greater degree in ER- carcinomas. However, the same region is equally hypomethylated in both ER+ and ER- cancer cell lines. Our results indicate that in breast carcinomas ER DNA methylation is deranged, and in cancer cell lines is different from that observed in primary tumours. Furthermore, the abnormal methylation in the 5' end seems to be related to abnormal expression, namely diffuse hypomethylation in carcinomas with high ER content and hypermethylation in carcinomas without ER. These findings support our previous hypothesis that DNA methylation could be involved in the control of ER gene expression and demonstrate that abnormal ER gene methylation is a typical feature of breast cancers.

This study reports the results of an evaluation of the effectiveness and tolerability of rifaximin, an intestinal topical antibiotic. It was administered using a nasogastric tube in patients with severe enterocolitis and bacterial superinfections causing intestinal inflammatory diseases and portosystemic encephalopathy. The drug proved highly effective clinically and produced neither local nor systemic side-effects.E’ stata valutata l'efficacia e la tollerabilita delia rifaximina, un antibiotico ad azione topica intestinale, somministrata tramite sondino nasogastrico in pazienti affetti da gravi enterocoliti, sovrainfezioni batteriche in corso di malattie infiammatorie intestinali ed encefalopatia porto-sistemica. Oltre all'ottima efficacia clinica si segnala l'assenza di effetti collaterali, locali e sistemici, di questo farmaco.

The present study was designed: (a) to compare the additional inspiratory laryngeal mask airway (LMA) resistance measured in vitro during simulated ventilation and in vivo in five anaesthetised and mechanically ventilated patients; and (b) to evaluate the resistive pressure drop along the length of the LMA. After the differential pressure across the mask was measured, the pressure-flow relationship was characterised by Rohrer's equation and in vitro and in vivo resistance was calculated. Thereafter, the distal pressure measuring point was moved along the length of the LMA and differential pressure was measured at each point under in vitro and in vivo conditions. Values for resistance were approximately twice as great in vivo as those obtained in vitro, with most of the resistive pressure drop occurring across the vertical bars, especially when measured in vivo. We conclude that in vivo positioning of the LMA significantly increases resistance because of the configurational changes occurring when the LMA is in situ.

The efficacy of spirapril, 6 mg once daily, was compared with enalapril, 5–20 mg once daily, in the control of mild-to-moderate hypertension in a placebo-controlled, parallel-group study. A total of 251 patients participated in the study, all of whom underwent a 4-week washout period on placebo. Thereafter, 100 patients were randomized to spirapril, 6 mg once daily, 101 patients to enalapril, 5–20 mg once daily, and 50 patients remained on placebo. Sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were measured at 2-weekly clinic visits. Blood pressure profiles during peak and trough plasma drug concentrations (2–4 hours and 24 hours postdose, respectively) were determined at baseline and 4 and 8 weeks after starting the double-blind phase. Compared with placebo, treatment with both spirapril and enalapril resulted in significant reductions (p > 0.001) in DBP and SBP. DBP was reduced to a greater extent with spirapril than with enalapril both at peak (−17.4 mmHg vs. −14.8 mmHg) and trough (−14.7 mmHg vs. −12.4 mmHg). Thus, although the trough/peak DBP ratios for spirapril and enalapril were very similar (84% vs. 82%), actual reductions in DBP were different. Spirapril and enalapril treatment resulted in similar reductions in SBP at both peak and trough levels. Both drugs were well tolerated, and there were very few adverse events or changes in hematological or biochemical parameters during the study. In conclusion, spirapril, 6 mg once daily, as the initial and maintenance dose, is at least as effective and well tolerated as enalapril individually titrated.