Cost-effectiveness analysis of intensity-modulated radiation therapy with normal and hypofractionated schemes for the treatment of localised prostate cancer.

The aim of our analysis was to compare the cost-effectiveness of high-dose intensity-modulated radiation therapy (IMRT) and hypofractionated intensity-modulated radiation therapy (HF-IMRT) versus conventional dose three-dimensional radiation therapy (3DCRT) for the treatment of localised prostate cancer. A Markov model was constructed to calculate the incremental quality-adjusted life years and costs. Transition probabilities, adverse events and utilities were derived from relevant systematic reviews. Microcosting in a large university hospital was applied to calculate cost vectors. The expected mean lifetime cost of patients undergoing 3DCRT, IMRT and HF-IMRT were 7,160 euros, 6,831 euros and 6,019 euros respectively. The expected quality-adjusted life years (QALYs) were 5.753 for 3DCRT, 5.956 for IMRT and 5.957 for HF-IMRT. Compared to 3DCRT, both IMRT and HF-IMRT resulted in more health gains at a lower cost. It can be concluded that high-dose IMRT is not only cost-effective compared to the conventional dose 3DCRT but, when used with a hypofractionation scheme, it has great cost-saving potential for the public payer and may improve access to radiation therapy for patients.

A horizontally polarizing liquid trap enhances the tabanid-capturing efficiency of the classic canopy trap.

Host-seeking female tabanid flies, that need mammalian blood for the development of their eggs, can be captured by the classic canopy trap with an elevated shiny black sphere as a luring visual target. The design of more efficient tabanid traps is important for stock-breeders to control tabanids, since these blood-sucking insects can cause severe problems for livestock, especially for horse- and cattle-keepers: reduced meat/milk production in cattle farms, horses cannot be ridden, decreased quality of hides due to biting scars. We show here that male and female tabanids can be caught by a novel, weather-proof liquid-filled black tray laid on the ground, because the strongly and horizontally polarized light reflected from the black liquid surface attracts water-seeking polarotactic tabanids. We performed field experiments to reveal the ideal elevation of the liquid trap and to compare the tabanid-capturing efficiency of three different traps: (1) the classic canopy trap, (2) the new polarization liquid trap, and (3) the combination of the two traps. In field tests, we showed that the combined trap captures 2.4-8.2 times more tabanids than the canopy trap alone. The reason for the larger efficiency of the combined trap is that it captures simultaneously the host-seeking female and the water-seeking male and female tabanids. We suggest supplementing the traditional canopy trap with the new liquid trap in order to enhance the tabanid-capturing efficiency.

Defining the concept of 'tick repellency' in veterinary medicine.

Although widely used, the term repellency needs to be employed with care when applied to ticks and other periodic or permanent ectoparasites. Repellency has classically been used to describe the effects of a substance that causes a flying arthropod to make oriented movements away from its source. However, for crawling arthropods such as ticks, the term commonly subsumes a range of effects that include arthropod irritation and consequent avoiding or leaving the host, failing to attach, to bite, or to feed. The objective of the present article is to highlight the need for clarity, to propose consensus descriptions and methods for the evaluation of various effects on ticks caused by chemical substances.

Insight into the hidden bacterial diversity of Lake Balaton, Hungary.

In the present study, the prokaryotic community structure of the water of Lake Balaton was investigated at the littoral region of three different points (Tihany, Balatonmáriafürdo and Keszthely) by cultivation independent methods [next-generation sequencing (NGS), specific PCRs and microscopy cell counting] to check the hidden microbial diversity of the lake. The taxon-specific PCRs did not show pathogenic bacteria but at Keszthely and Máriafürdo sites extended spectrum beta-lactamase-producing microorganisms could be detected. The bacterial as well as archaeal diversity of the water was high even when many taxa are still uncultivable. Based on NGS, the bacterial communities were dominated by Proteobacteria, Bacteroidetes and Actinobacteria, while the most frequent Archaea belonged to Woesearchaeia (Nanoarchaeota). The ratio of the detected taxa differed among the samples. Three different types of phototrophic groups appeared: Cyanobacteria (oxygenic phototrophic organisms), Chloroflexi (anaerobic, organotrophic bacteria) and the aerobic, anoxic photoheterotrophic group (AAPs). Members of Firmicutes appeared only with low abundance, and Enterobacteriales (order within Proteobacteria) were present also only in low numbers in all samples.

A new look at transudation: the apocrine connection.

Transcellular trafficking in which various molecules are transported across the interior of a cell, is commonly classified as transcytosis. However, historically this term has been used synonymously with transudation. In both cases transcellular trafficking starts with the internalization of proteins or other compounds on the basal or basolateral side of a cell and continues by their transport across the interior to the apical pole (or vice versa) where they are subsequently released. This allows a cell to release products which are synthesized elsewhere. Here, we discuss the common features of both transcytosis and transudation, and that which differentiates them. It appears that transcytosis and transudation are identical in terms of vesicular import and endosomal sorting of cargo, but completely differ in the re-secretion process. Specialized epithelial cells re-release substantial quantities of the endocytosed material, and often also a great variety. Some recent studies indicate that this is achieved by non-canonical apocrine secretion rather than by the regular vesicular mechanism of exocytosis, and takes place only on the apical pole. This massive re-release of endocytosed proteins, and potentially other compounds via the apocrine mechanism should be considered as transudation, distinct from transcytosis.

Influence of biotope on the distribution and peak activity of questing ixodid ticks in Hungary.

In order to update the occurrence of hard tick species in Hungary, 3442 questing ticks were collected from the vegetation by the dragging/flagging method in 37 different places in the country, between March and June of 2007. Ixodes ricinus (L.) turned out to be ubiquitous. Dermacentor marginatus (Schulzer) was absent from sampling sites in the southwestern part of the country, but in most places was concomitant and contemporaneous with Dermacentor reticulatus (Fabricius). These two species, as well as I. ricinus, occurred up to an altitude of 900-1000 m a.s.l. Haemaphysalis inermis (Birula) and Haemaphysalis concinna (Koch) were not confined to any parts of the country, unlike Haemaphysalis punctata (Canestrini & Fanzago) which was found in only one region. The local prevalence of the latter species was also significantly lower than those of the former two in the same habitat (fringes of meadows, paths in forests). Dermacentor spp. and H. inermis were represented only by adults. In most species females were collected more frequently than males, except in H. concinna and H. punctata. Temporal differences between the peak activity of I. ricinus and Dermacentor spp. on dry pastures appeared to equalize on meadows in mountain forests, and a similar phenomenon was observed for the three Haemaphysalis spp. when collected along forest paths with fresh, green vegetation.

Prevalence of flea infestation in dogs and cats in Hungary combined with a survey of owner awareness.

A survey was conducted in order to gain current information on flea species (Siphonaptera: Pulicidae) infesting dogs and cats living in urban and rural areas of Hungary, along with data on the factors that affect the presence, distribution and seasonality of infestation. In addition, owner awareness of flea infestation was evaluated. Practitioners in 13 veterinary clinics were asked to examine all dogs and cats attending the clinic and to collect fleas, when present, on 2 days in each month from December 2005 to November 2006. They also completed a questionnaire for each animal examined. A total of 319 dogs (14.1%) were found to be infested; the highest prevalence (27.1%) of infestation on dogs occurred in August and the lowest (5.4%) in May. Prevalence of fleas on cats was higher (22.9%); the highest (35.0%) and lowest (8.1%) prevalences occurred in July and April, respectively. Fleas were more prevalent in rural (387/1924 animals, 20.2%) than in urban (161/1343 animals, 12.0%) areas. Three species, Ctenocephalides felis (Bouché), Ctenocephalides canis (Curtis) and Pulex irritans L., were found. On dogs, the prevalence of C. canis alone was 53.0%, whereas that of C. felis alone was 36.0%. Only 19 specimens of P. irritans were found on 14 dogs from rural habitats only. Prevalence of C. felis only on cats was 94.3%; the remaining cats were infested with either C. canis or with mixed infestations of C. felis and C. canis. More than half (51.4%) of the owners of infested dogs and cats had not used flea control products in the past year or more, and five times as many owners in rural than urban areas had not used flea control products in the same period. Very few owners reported having attempted to kill fleas in their animals' environment; instead, they believed that fleas were acquired from other cats or dogs.

Traumatic myiasis in dogs caused by Wohlfahrtia magnifica and its importance in the epidemiology of wohlfahrtiosis of livestock.

In the province of Al Hoceima, northern Morocco, and on two farms in Hungary, dogs were inspected for the presence of traumatic myiasis. Nine and four infested dogs were found in Morocco and Hungary, respectively. All the larvae and adults reared from them in the laboratory were identified as Wohlfahrtia magnifica (Schiner) (Diptera: Sarcophagidae). To our knowledge, these are the first cases of wohlfahrtiosis in dogs to be reported in these countries. All infested animals lived close to livestock, where wohlfahrtiosis was endemic. Infested body sites included limbs (six cases), external genitalia (two), ears (three), nose (one) and neck (one). Developing larvae caused severe welfare problems and tissue destruction in most cases. Although the number of cases reported here is small, wohlfahrtiosis in dogs may be very important from an epidemiological perspective because farm and stray dogs can act as both reservoirs and carriers of this parasitic fly species. Therefore, education of dog owners concerning the risk factors in endemic regions is recommended in order to reduce the prevalence of wohlfahrtiosis in dogs and thereby in livestock. Both owners and veterinarians should pay regular attention to any wounds and to the natural orifices of dogs, especially during the fly seasons.

Morphological and mitochondrial DNA characters for identification and phylogenetic analysis of the myiasis-causing flesh fly Wohlfahrtia magnifica and its relatives, with a description of Wohlfahrtia monegrosensis sp. n. Wyatt & Hall.

Wohlfahrtia magnifica (Schiner) (Diptera: Sarcophagidae) is a major cause of traumatic myiasis in livestock in Central and Eastern Europe and in countries bordering the Mediterranean. The present study explored the utility of external body characters, genitalia characters and mitochondrial DNA characters for identification of this and related species in the subfamily Paramacronychiinae. Sequence analyses of the 3' terminal 273 bp of the mitochondrial cytochrome b gene revealed two lineages of W. magnifica, one from Spain and France and the other from the rest of Eurasia, differing by only two base pairs. Phylogenetic analysis of cytochrome b showed that W. magnifica and Wohlfahrtia vigil Walker were sister species; this conclusion was not contradicted by a phylogenetic analysis of the morphological characters. Based on cytochrome b, the genetic distance between specimens of W. vigil from Europe and North America was sufficiently large to justify the recognition of more than one species. A new species, Wohlfahrtia monegrosensis, from northern Spain, was described, based on morphology and cytochrome b. A unique combination of external body characters of males or females were diagnostic for W. magnifica, the W. vigil group and Wohlfahrtia bella, but only the genitalia characters were diagnostic for all nine species studied.

Molecular genetic analysis of populations of Wohlfahrt's wound myiasis fly, Wohlfahrtia magnifica, in outbreak populations from Greece and Morocco.

Wohlfahrt's wound myiasis fly, Wohlfahrtia magnifica (Schiner) (Diptera: Sarcophagidae), is the most important cause of traumatic myiasis in the southern Palaearctic region. Larval stages are obligate parasites and the wounds caused by infestations are very similar to those caused by Old and New World screwworm flies. During the last decade, W. magnifica appears to have expanded its range to parts of northern and central Morocco, and to Crete, Greece. Specimens of W. magnifica were collected in Morocco and Crete either as larvae (preserved in 80% ethanol) or as adults (dry-pinned). Comparison specimens were collected in Spain, Hungary and mainland Greece. A DNA fragment containing the 3' 715 base pairs of the mitochondrial cytochrome b gene was amplified by polymerase chain reaction from each of 132 larvae or adults of W. magnifica and the amplicons were directly sequenced and analysed phylogeographically. Twelve cytochrome b haplotypes were detected. All haplotypes from Morocco belonged to a lineage that included specimens from the Iberian peninsula, and restricted mixing of central and northern populations in Morocco was demonstrated. Cytochrome b haplotyping combined with an analysis of larval size provided clear evidence of multiple infestations of hosts in all geographical areas, with one quarter of wounds containing larvae from two to at least four females. More than 80% of specimens from Crete contained a haplotype predominating in mainland Greece and Hungary. Our survey indicated that wohlfahrtiosis was more widespread in northern and central Morocco than previously recorded by government veterinarians. However, the prevalence of wohlfahrtiosis was low (< 1%). The high genetic diversity of Moroccan populations is consistent with longterm endemicity, rather than recent introduction. Crete showed a higher prevalence of wohlfahrtiosis (< or = 15%) and less genetic diversity of W. magnifica, which is consistent with a recent introduction. The western and eastern Mediterranean lineages may have been isolated in different Pleistocene ice-age refugia, from which there has been limited post-glacial dispersal.

Molecular investigations of cat fleas (Ctenocephalides felis) provide the first evidence of Rickettsia felis in Malta and Candidatus Rickettsia senegalensis in Israel.

Rickettsia felis, the causative agent of flea-borne spotted fever, occurs on all continents except Antarctica, owing to the cosmopolitan distribution of its cat flea vector. In this study, cat fleas were collected in two countries where the occurrence of R. felis was either unknown (Malta) or where accurate prevalence data were lacking (Israel). Altogether 129 fleas were molecularly analysed for the presence of rickettsial DNA. On the basis of three genetic markers, R. felis was identified in 39.5% (15/38) of the cat fleas from Malta. Sequences showed 100% identity to each other and to relevant sequences in GenBank. Among the 91 cat fleas from Israel, two (2.2%) contained the DNA of Candidatus Rickettsia senegalensis. Phylogenetically, the R. felis and Candidatus R. senegalensis identified here clustered separately (with high support) but within one clade, which was a sister group to that formed by the typhus group and spotted fever group rickettsiae. This is the first record of R. felis in Malta and of Candidatus R. senegalensis outside its formerly reported geographical range including Africa, Asia and North America.

Prevalence of Setaria equina microfilaraemia in horses in Hungary.

Peripheral blood samples were collected randomly from 195 horses in various parts of Hungary, and the presence of microfilariae was evaluated by the Knott technique. On the basis of morphological identification 18 of the horses (9.2 per cent) were infected with Setaria equina, and the infection was confirmed in 10 animals by pcr and sequencing. The level of microfilaraemia was between 1 and 1138 larvae in 2 ml of blood. There was no correlation between the time of sampling or the sex of the animals (stallions versus mares) and the prevalence of infection, but the prevalence decreased with age. There was a significant association between the prevalence of microfilaraemia and the presence of still waters; positive samples were collected either in the region of Lake Balaton, the largest lake in the country, or at places with nearby ponds.

Serological evidence for Babesia canis infection of horses and an endemic focus of B. caballi in Hungary.

In order to evaluate the seroconversion of horses to Babesia caballi and B. canis in Hungary, blood samples were collected from 371 animals on 23 different locations of the country. The presence of antibodies to B. caballi was screened with a competitive ELISA. All 29 positive samples came from one region (the Hortobágy). The prevalence of infection did not show correlation with sexes, and reached 100% in the age group of 2-5 years. Babesia canis-specific antibodies were demonstrated by IFAT in 6.74% of animals kept in 7 regions. The titres were low or medium level (1:40 to 1:160), indicating that the horses had previously been exposed to this piroplasm, but their infection must have been limited. The highest seropositivity rate was observed in the age group of 3-4 years, and males (stallions and geldings) were significantly more frequently infected than females. However, neither B. caballi nor B. canis could be identified in the peripheral blood samples of infected horses by PCR. Since most of the B. caballi-positive horses remained negative in the B. canis IFAT, whereas seroconversion solely to B. canis was detected in several regions of the country, serological cross-reaction between the two species can be discounted. This is the first serological evidence of horses being naturally infected with B. canis, supporting the view that piroplasms are less host specific than previously thought.

Canine neosporosis in Hungary: screening for seroconversion of household, herding and stray dogs.

In order to assess the seroprevalence of canine neosporosis 651 blood samples were collected from 586 household, 41 herding and 24 stray dogs, at small animal clinics in four large cities and other places of Hungary. Nineteen (2.9%) showed positivity in the IFAT with titres between 1:80 and 1:10240. Two dogs with high titres of antibodies to Neospora caninum had neuromuscular signs (imbalance, tremor) and a further one developed papulomatous, ulcerative and necrotizing dermatitis. There was no correlation between titers and age, sex, breed or keeping place. Although more male dogs had antibodies to N. caninum than females in case of both household and herding dogs, this association was not significant. No breed predisposition was observed. However, dogs with seroconversion were significantly more prevalent among rural (6%) than among urban dogs (1%), indicating that dogs in the countryside may have contact with or access to potentially infected offal from cattle and other intermediate hosts more frequently than those in large cities. Furthermore, significantly more herding dogs (29.3%) had antibodies to N. caninum than household dogs (1.2%), confirming the association between the occurrence of neosporosis and dog keeping on farms. The 12 dogs found seropositive among herding ones lived on 6 farms, on 5 of which seropositive cattle were also identified. This is the first report on the prevalence of N. caninum infection in dogs in Hungary.

Local distribution and concentration of intravenously injected 131I-9.2.27 monoclonal antibody in human malignant melanoma.

Regional measurements of 131I-9.2.27 distribution in human melanoma tumors were obtained using quantitative autoradiography. Tumors were removed from patients 72-96 h after they had received an i.v. injection of 9.15 mCi (100 mg) of 131I-9.2.27. The autoradiographic images showed that the radioactivity reaching the tumor was heterogeneously distributed. Areas of relative high and low uptake were selected in each tumor. Regions of high activity contained from 51 to 1371 nCi/g, while areas with low uptake had radioactivity ranging from 12 to 487 nCi/g. The reliability of the autoradiographic measurements was demonstrated by the strong positive correlation with direct tissue sample counting (r = 0.994 P less than 0.001). Since comparative immunocytochemistry showed a homogeneous and diffuse staining of target antigen on viable tumor cells, variability of monoclonal antibody uptake within individual tumors was not primarily due to heterogeneity of antigen expression in these cases. However, antigen levels accounted for some of the variation from tumor to tumor. When immunoperoxidase staining was repeated on adjacent sections without the addition of 9.2.27, it confirmed the nonuniform distribution of monoclonal antibody found at autoradiography. Thus, quantitative autoradiography gives information about the distribution and the local concentration of radioactive antibody in tumors allowing calculation of the radiation dose delivered to small regions within tumors.

The timing of drosophila salivary gland apoptosis displays an l(2)gl-dose response.

During Drosophila metamorphosis, larval tissues, such as the salivary glands, are histolysed whereas imaginal tissues differentiate into adult structures forming at eclosion a fly-shaped adult. Inactivation of the lethal(2)giant larvae (l(2)gl) gene encoding the cytoskeletal associated p127 protein, causes malignant transformation of brain neuroblasts and imaginal disc cells with developmental arrest at the larval-pupal transition phase. At this stage, p127 is expressed in wild-type salivary glands which become fully histolysed 12 - 13 h after pupariation. By contrast to wild-type, administration of 20-hydroxyecdsone to l(2)gl-deficient salivary glands is unable to induce histolysis, although it releases stored glue granules and gives rise to a nearly normal pupariation chromosome puffing, indicating that p127 is required for salivary gland apoptosis. To unravel the l(2)gl function in this tissue we used transgenic lines expressing reduced ( approximately 0.1) or increased levels of p127 (3.0). Here we show that the timing of salivary gland histolysis displays an l(2)gl-dose response. Reduced p127 expression delays histolysis whereas overexpression accelerates this process without affecting the duration of third larval instar, prepupal and pupal development. Similar l(2)gl-dependence is noticed in the timing of expression of the cell death genes reaper, head involution defective and grim, supporting the idea that p127 plays a critical role in the implementation of ecdysone-triggered apoptosis. These experiments show also that the timing of salivary gland apoptosis can be manipulated without affecting normal development and provide ways to investigate the nature of the components specifically involved in the apoptotic pathway of the salivary glands.

The LAMMER protein kinase encoded by the Doa locus of Drosophila is required in both somatic and germline cells and is expressed as both nuclear and cytoplasmic isoforms throughout development.

Activity of the Darkener of apricot (Doa) locus of Drosophila melanogaster is required for development of the embryonic nervous system, segmentation, photoreceptor maintenance, normal transcription, and sexual differentiation. The gene encodes a protein kinase, with homologues throughout eukaryotes known as the LAMMER kinases. We show here that DOA is expressed as at least two different protein isoforms of 105 and 55 kD throughout development, which are primarily localized to the cytoplasm and nucleus, respectively. Doa transcripts and protein are expressed in all cell types both during embryogenesis and in imaginal discs. Although it was recently shown that DOA kinase is essential for normal sexual differentiation, levels of both kinase isoforms are equal between the sexes during early pupal development. The presence of the kinase on the cell membrane and in the nuclei of polytene salivary gland cells, as well as exclusion from the nuclei of specific cells, may be indicative of regulated kinase localization. Mosaic analysis in both the soma and germline demonstrates that Doa function is essential for cell viability. Finally, in contrast to results reported in other systems and despite some phenotypic similarities, genetic data demonstrate that the LAMMER kinases do not participate in the ras-MAP kinase signal transduction pathway.

Wohlfahrtiosis in sheep and the role of dicyclanil in its prevention.

Wohlfahrtia magnifica is the main agent of traumatic myiasis in the southern Palaearctic zone. It was recorded in outbreak situations in Crete, Greece, for the first time in 1999, causing widespread production losses and considerable concern in the livestock sectors. Most commonly applied curative insecticides, organophosphates and pyrethroids, can kill larvae of W. magnifica, but they do not provide long-term protection from infestation or re-infestation, which would facilitate wound healing. The objective of the present work was to study the seasonal dynamics of sheep wohlfahrtiosis in Crete and to determine the prophylactic efficacy of dicyclanil, an insect growth regulator, against natural infestations by larvae of W. magnifica. Six sheep flocks were studied, three from a semi-intensive husbandry system and three from an extensive husbandry system. Two flocks were kept as untreated controls and also were used to study the disease dynamics. Dicyclanil was strategically applied just to males and young non-milking females in four treatment flocks; milking females in these flocks were not treated. The untreated flocks demonstrated seasonal patterns in case numbers that were associated with changes in climate and husbandry activities, especially reproduction and shearing. Cases were most common on the genitalia (60%) and a greater proportion of males than females were infested. The prophylactic efficacy of dicyclanil in males was up to 91.3% over the entire trial period. Hence the incidence in treated males at 22 weeks, when final infestations were recorded, was 5-10% compared to 45-55% in untreated controls. Moreover, the application of dicyclanil to a limited number of animals per flock (males and non-milking females=c. 15-20% of the flock) significantly reduced the incidence of wohlfahrtiosis even in the untreated animals. Hence, final overall incidences in the treated flocks ranged from 4.5 to 5.5% compared to 13.3-13.4% in the control flocks.

Evaluation of efficacy of entomopathogenic nematodes against larvae of Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae).

The blowfly Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae) is the primary agent of cutaneous myiasis of sheep in northern Europe, southern Africa, Australia and New Zealand. As the application of chemicals has several disadvantages, alternative control measures of traumatic myiasis of livestock must be developed. In this study, the use of entomopathogenic nematodes (EPNs) as potential biocontrol agents against second instar larvae of Lucilia sericata was considered. The following nematode species were tested: Heterorhabditis bacteriophora (IS 5, HHU 1, Hmol, HNC 1, HAZ 36, Hbrecon, HHU 2, HAZ 29, HHP 88, HHU 3, HHU 4 and HGua), Steinernema intermedia, NC513 strain of S. glaserii, S. anomali, S. riobrave, Steinernema sp. and 5 strains of S. feltiae (22, Vija Norway, HU 1, scp, and IS 6). None of the examined EPN species or strains showed larvicidal efficacy at 37 degrees C (no killing effect was observed in the case of the two heat-tolerant strains--H. bacteriophora and S.feltiae) against L. sericata larvae. At lower temperatures (20 degrees C and 25 degrees C) only strains of S. feltiae were found to be active. The overall odds ratios calculated for L. sericata maggots to contract S. feltiae nematode infection show significant (p < 0.05) effect only in the case of strains HU 1, 22 and IS 6. In the case of strains HU 1 and 22 parasitic forms of S. feltiae could be detected in the dead larvae of L. sericata. Strain IS 6 (and also Vija Norway at 20 degrees C) penetrated and killed fly larvae, but only adult forms of the nematode occurred in the cadavers.

Vasodilators and regression of left ventricular hypertrophy. Hydralazine versus prazosin in hypertensive humans.

Long-term treatment of hypertensive rats with arterial vasodilators may further increase left ventricular hypertrophy. Since left ventricular hypertrophy may be an important determinant of outcome in hypertension, the long-term effects of arterial vasodilation with hydralazine on left ventricular mass and function were compared with those of an alternative third-line drug, the alpha1 blocker prazosin, in patients still hypertensive despite combined diuretic and beta blocker therapy. A single-blind, randomized, two-group parallel design was employed. Both treatments induced a sustained antihypertensive effect, with hydralazine showing more effect on supine blood pressure, and prazosin having more effect on standing pressure. Heart rate, cardiac output, and volume status showed only minor changes. Plasma norepinephrine showed a sustained increase when measured in both the supine and standing positions, but the increases were similar for the two treatments. Supine and standing plasma renin activity increased only during long-term treatment with hydralazine. Prazosin induced a progressive decrease in left ventricular mass over time (-34 +/- 15 g/m2 at 12 months), but hydralazine did not (-9 +/- 10 g/m2 after 12 months). Stepwise regression indicated that a decrease in systolic blood pressure was associated with a decrease in left ventricular mass with both treatments, but an increase in plasma norepinephrine was associated with an increase in left ventricular mass only with hydralazine, suggesting that increased sympathetic activity may affect left ventricular mass via cardiac alpha1 receptors. Thus, if regression of left ventricular hypertrophy is a worthwhile therapeutic goal, hydralazine and analogous arterial vasodilators are not drugs of choice.