Thermal desorption as a high removal remediation technique for soils contaminated with per- and polyfluoroalkyl substances (PFASs).

Soils contaminated with per- and polyfluoroalkyl substances (PFASs) are an important source for impacting drinking water delivery systems and surface water bodies world-wide, posing an urgent risk to human health and environmental quality. However, few treatment techniques have been tested for PFAS-contaminated soil hotspots. This study investigated the possibility of thermal desorption as a possible technique to remediate soils contaminated with multiple PFASs. Two fortified soils (∑9PFAS ≈ 4 mg kg-1) and one field-contaminated soil (∑9PFAS ≈ 0.025 mg kg-1) were subjected to a 75-min thermal treatment at temperatures ranging from 150 to 550°C. Soil concentrations of PFASs showed a significant decrease at 350°C, with the ∑9PFAS concentration decreasing by, on average, 43% and 79% in the fortified and field contaminated soils, respectively. At 450°C, >99% of PFASs were removed from the fortified soils, while at 550°C the fraction removed ranged between 71 and 99% for the field contaminated soil. In the field contaminated soil, PFAS classes with functional groups of sulfonates (PFSAs) and sulfonamides (FOSAs) showed higher removal than the perfluoroalkyl carboxylates (PFCAs). Thus thermal desorption has the potential to remove a wide variety of PFASs from soil, although more studies are needed to investigate the cost-effectiveness, creation of transformation products, and air-phase vacuum filtration techniques.

Impulsive suicide attempts among young people-A prospective multicentre cohort study in Sweden.

BACKGROUND: We aimed to compare the prevalence of impulsive suicide attempts (ISA) among young adults and those over 25 who present at hospital in connection with attempted suicide. We also aimed to identify factors associated with ISA in young adults and to assess medical severity as well as the probability of repeated suicide attempts in this age group. METHOD: A prospective multicentre cohort study included hospital known cases of suicide attempt (N = 666). The prevalence of ISA was compared between young adults (18-25) and adults aged > 26. We used logistic regression models to identify factors associated with ISA, associations of ISA with high medical severity and prediction of new fatal or non-fatal suicide attempts within 6 months. RESULTS: 43.7% of the young patients had made an ISA, and 30.2% among those aged > 26 (p = 0.001). Among the young, substance use disorder was associated with ISA; crude odds ratio (OR) 2.0 (1.0-4.2), and adjusted OR 2.1 (0.99-4.4). Affective disorder and unemployment/ sickness absence implied lower odds of ISA. ISA resulted in injuries of high medical severity as often as more planned attempts and non-fatal or fatal repetition within 6 months was equally common (30%) in both groups. LIMITATIONS: The study was set in psychiatric emergency services, which limits the generalizability. CONCLUSIONS: Clinicians should acknowledge that suicide attempts among youth often occur without previous planning and may result in medically severe injuries. The probability of new fatal or non-fatal suicide attempts should be kept in mind also after an impulsive suicide attempt.

Enriched cages for groups of laboratory male rats and their effects on behaviour, weight gain and adrenal glands.

We investigated if there were any negative effects on the behaviour and physiology of rats housed in groups of five in two types of enriched cages and compared them with paired-housed rats housed in traditional cages. Eighty-four male Wistar and Sprague-Dawley rats were housed in an enriched rat cage (ERC), a rebuilt rabbit cage (RRC) or a Makrolon III cage (MC) system from 5-16 weeks of age with access to different enrichments. Recordings of behaviour and cage use (3 × 24 h video recording), weekly weighing, measuring food consumption four days/week and water consumption two days/week, were carried out. The rats' muscle strength was assessed using the 'inclined plane' at the end of the study, and after euthanasia the adrenal glands were removed and weighed. Being in the shelter was the most common behaviour in the ERC and RRC groups. In the MC group, which lacked a shelter, rats performed the highest percentage of lying, grooming, rearing, play fighting and manipulating paper shreds. Rats in the RRC had the highest percentage of standing and manipulating gnawing sticks. Water consumption was higher in MC than in ERC and RRC rats. Rats from the RRC managed to remain at a steeper angle on the 'inclined plane' than rats from the MC. There were no significant effects of cage type on weight gain, food consumption or relative weights of adrenal glands. In conclusion, male rats kept in groups of five in larger enriched cages benefited from the enrichments, and no negative effects were found in the larger groups.

Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk.

The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.

Sodium bicarbonate improves swimming performance.

Sodium bicarbonate ingestion has been shown to improve performance in single-bout, high intensity events, probably due to an increase in buffering capacity, but its influence on single-bout swimming performance has not been investigated. The effects of sodium bicarbonate supplementation on 200 m freestyle swimming performance were investigated in elite male competitors. Following a randomised, double blind counterbalanced design, 9 swimmers completed maximal effort swims on 3 separate occasions: a control trial (C); after ingestion of sodium bicarbonate (SB: NaHCO3 300 mg . kg (-1) body mass); and after ingestion of a placebo (P: CaCO3 200 mg . kg (-1) body mass). The SB and P agents were packed in gelatine capsules and ingested 90 - 60 min prior to each 200 m swim. Mean 200 m performance times were significantly faster for SB than C or P (1 : 52.2 +/- 4.7; 1 : 53.7 +/- 3.8; 1 : 54.0 +/- 3.6 min : ss; p < 0.05). Base excess, pH and blood bicarbonate were all elevated pre-exercise in the SB compared to C and P trials (p < 0.05). Post-200 m blood lactate concentrations were significantly higher following the SB trial compared with P and C (p < 0.05). It was concluded that SB supplementation can improve 200 m freestyle performance time in elite male competitors, most likely by increasing buffering capacity.

IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients.

SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.

RAD51C (RAD51L2) is involved in maintaining centrosome number in mitosis.

The RAD51C (RAD51L2) protein is one out of five RAD51 paralogs and forms a complex that includes either XRCC2 or XRCC3. Both of these complexes may have important functions in homologous recombination (HR). Here, we confirm that the frequency of DNA double-strand break (DSB)-induced HR is reduced in the RAD51C deficient cell line CL-V4B, in agreement with a role for RAD51C in HR. We report that mitotic RAD51C deficient CL-V4B cells also have an increased number of centrosomes in mitosis resulting in aberrant mitotic spindles. These data suggest that the RAD51C protein is important in maintaining correct centrosome numbers and that the complexes including RAD51C and XRCC2 or XRCC3 may be of importance in maintaining correct centrosome numbers in mitosis. Increased centrosome numbers following a RAD51C defect indicates that this protein might be important in preventing aneuploidy, suggesting that it could be a potential tumour suppressor in mammals.

Cost-effectiveness of formoterol and salbutamol as asthma reliever medication in Sweden and in Spain.

This study aimed to evaluate the cost-effectiveness of formoterol (Oxis) Turbuhaler 4.5 microg and salbutamol 200 microg as reliever medications in Sweden and Spain. The study used data on effectiveness (exacerbations and symptom-free days) and resource utilisation from an open, 6-month, parallel-group, multicentre randomised trial with 18,124 asthma patients in 24 countries. Country-specific unit costs for Sweden and for Spain were used to transform resource utilisation data into costs. Total healthcare costs were not significantly different between formoterol and salbutamol dry powder inhalers in Sweden, whereas in Spain, the healthcare costs were 20% higher for formoterol vs. salbutamol pressurised metered dose inhalers. Total healthcare costs increased with disease severity, defined according to the Global Initiative for Asthma guidelines. Compared with salbutamol, formoterol produced statistically significant improvements in effectiveness, less reliever and maintenance medication usage, reduced healthcare resource utilisation, with no increase or a limited increase in healthcare cost.

Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial.

The aim of the study was to compare the safety and effectiveness of as-needed formoterol with salbutamol in a large international real-life asthma study. Children and adults (n=18,124) were randomised to 6 months as-needed treatment with open-label formoterol 4.5 microg Turbuhaler or salbutamol 200 microg pressurised metered dose inhaler or equivalent. Primary safety variables were asthma-related and nonasthma-related serious adverse events (SAE)s and adverse events (AE)s resulting in discontinuation (DAE)s. The primary efficacy variable was time to first asthma exacerbation. The incidences of AEs, SAEs and DAEs arising from SAEs were not significantly different between treatments. DAEs for nonserious AEs were higher with formoterol. Asthma-related AEs decreased with formoterol (1,098 (12.3%) versus 1,206 (13.5%)), asthma-related SAEs were similar (108 (1.2%) versus 121 (1.4%)) but more asthma-related DAEs occurred in the formoterol group (89 (1.0%) versus 48 (0.5%)). Time to first exacerbation was prolonged (hazard ratio 0.86) and less as-needed and maintenance medication was used with formoterol. Reductions of exacerbations with as-needed formoterol versus salbutamol increased with increasing age and asthma medication level. This real-life study demonstrates that formoterol as-needed has a similar safety profile to salbutamol, and its use as a reliever therapy is associated with fewer asthma symptoms and exacerbations.

A carbohydrate-rich drink reduces preoperative discomfort in elective surgery patients.

UNLABELLED: We studied the effects of different preoperative oral fluid protocols on preoperative discomfort, residual gastric fluid volumes, and gastric acidity. Two-hundred-fifty-two elective abdominal surgery patients (ASA physical status I-II) were randomized to preparation with a 12.5% carbohydrate drink (CHO), placebo (flavored water), or overnight fasting. The CHO and Placebo groups were double-blinded and were given 800 mL to drink on the evening before and 400 mL on the morning of surgery. Visual analog scales were used to score 11 different discomfort variables. CHO did not increase gastric fluid volumes or affect acidity, and there were no adverse events. The visual analog scale scores in a control situation were not different between groups. During the waiting period before surgery, the CHO-treated group was less hungry and less anxious than both the other groups (P < or = 0.05). CHO reduced thirst as effectively as placebo (P < 0.0001 versus Fasted). Trend analysis showed consistently decreasing thirst, hunger, anxiety, malaise, and unfitness in the CHO group (P < 0.05). The Placebo group experienced decreasing unfitness and malaise, whereas nausea, tiredness, and inability to concentrate increased (P < 0.05). In the Fasted group, hunger, thirst, tiredness, weakness, and inability to concentrate increased (P < 0.05). In conclusion, CHO significantly reduces preoperative discomfort without adversely affecting gastric contents. IMPLICATIONS: Discomfort during the period of waiting before elective surgery can be reduced if patients are prepared with a carbohydrate-rich drink, compared with preoperative oral intake of water or overnight fasting. Visual analog scales can provide useful information about preoperative discomfort in elective surgery patients.

Is transient lumbar pain after spinal anaesthesia with lidocaine influenced by early mobilisation?

BACKGROUND: The aetiology of transient lumbar pain (TLP) after spinal anaesthesia has generated much interest. Many theories have been discussed. Early ambulation has been suggested as one plausible theory for developing TLP. METHODS: A total of 107 patients scheduled for inguinal hernial repair under spinal anaesthesia (20 mg/ml hyperbaric lidocaine) were randomised to either early or late ambulation: the early ambulation (group A), as early as possible after total regression of spinal block or the late mobilisation (group B) bedridden for more than 12 h. The clinical course and duration of operation were monitored. Assessments 4, 8 and 12 h after spinal anaesthesia were performed with respect to wound pain, nausea, tiredness and eventual symptoms of TLP were recorded. The patients also kept a diary about any symptoms once daily day 1-3 at home. A telephone follow-up was performed at day 5-7. RESULTS: Our results showed an incidence of TLP of 23% in all patients. No difference was recorded between early and late mobilisation patients, 12 and 13 patients, respectively. CONCLUSION: Early ambulation does not seem to increase the risk of developing TLP.

Normal tissue response to low doses of radiotherapy assessed by molecular markers--a study of skin in patients treated for prostate cancer.

The aim of this study was to evaluate normal tissue response by molecular markers to multifraction low doses of ionizing radiation, with the focus on changes in repopulation, estimated using Ki-67 as the proliferation marker, and on expressions of the p53 and p21 proteins, identified as key proteins in the DNA damage checkpoint. Repeated skin biopsies were taken from patients treated for prostate cancer with radiotherapy. The expressions of Ki-67, p53 and p21 of the keratinocytes in the basal cell layer of the epidermis were quantified immunohistochemically. The dose to the basal layer was 1.1 Gy per fraction, given five times per week for seven weeks. The indices of the three markers were determined over the whole period. A significant suppression of the Ki-67 index was observed during the first weeks, followed by a significant gradual increase in the Ki-67 index over the last weeks. The p53 and p21 protein levels were almost zero in the unirradiated skin. Upon irradiation, both the p53 and p21 index increased in a pattern very congruent to the Ki-67 index. In conclusion, daily fractions of about 1 Gy to the skin resulted in, for the keratinocytes in the basal layer, a cell growth arrest for a couple of weeks and a subsequent acceleration in repopulation during the following weeks of irradiation. The present findings also provided novel insights into the role of the p53/p21 pathway in the response of a normal epithelium to ionizing radiation as it is applied in radiotherapy.

The importance of osmolality for intermittent catheterization of the urethra.

OBJECTIVES: The urethral trauma after catheterization with intermittent catheters was studied histologically using unconscious rabbits. SETTING: The study was performed at Astra Hässle, Mölndal, Sweden. MATERIALS AND METHODS: Fifteen rabbits were randomized into five groups (three rabbits in each group), one control group and four groups catheterized with four different LoFric catheters (Astra Tech, Mölndal, Sweden): (1) control (not catheterized); (2) salt coated (i.e. high osmolality catheters) with drainage eyes; (3) without salt (i.e. low osmolality catheters) and with eyes; (4) with salt coating but without drainage eyes; and (5) without neither salt coating nor drainage eyes. The urethral injuries were evaluated using a four graded histological scale. RESULTS: The results showed that salt coated LoFric catheters gave less urethral trauma than LoFric catheters without salt. This was also supported by the significantly lower removal friction measured during withdrawal of the high osmolality catheters. No significant differences either in removal friction or in urethral trauma could be observed between LoFric catheters with or without drainage eyes. CONCLUSION: It may be concluded that osmolality is one important factor (there might be others, like e.g. water binding ability) when comparing different hydrophilic catheters, in regards to removal friction and urethral trauma. Furthermore it is suggested that there is no difference in urethral trauma between catheters with eyes or without eyes. To minimize the risk of urethral trauma, high osmolality catheters are recommended, especially when the catheterization times are a few minutes or more.

A retrospective analysis of nitric oxide inhalation in patients with severe acute lung injury in Sweden and Norway 1991-1994.

BACKGROUND: Patients with severe acute lung injury (ALI) have been treated compassionately on doctors' initiative with inhaled nitric oxide (INO) in Sweden and Norway since 1991. In 1994 the previously used technical grade nitric oxide was replaced by medical grade nitric oxide. METHODS: We have carried out a retrospective data collection on all identified adult patients treated with INO for >4 h during the period 1991-1994 focusing on safety aspects and patient outcome. We used the following exclusion criteria (1) Age <18 years, (2) Simultaneous treatment with extracorporeal removal of CO2 (3) NO inhalation period <4 h, (4) Incomplete or missing patient charts, (5) Use of INO in order to treat pulmonary hypertension following cardiac surgery, with little or no acute lung injury. RESULTS: Inclusion criteria were met by 56 out of 73 identified patients. Mean age was 48+/-19 years and the median duration of INO treatment was 102 h. PaO2/FIO2 ratio at start of treatment was 85 +/- 33 mm Hg with a lung injury score (LIS) of 3.2+/-0.8. The aetiology of the lung injury was pneumonia (n= 27), sepsis (n=12) and trauma (n=8). Survival to hospital discharge was 41% and survival after 180 d was 38%. Three serious adverse events were identified, two from technical failures of the INO delivery device and one withdrawal reaction necessitating slow weaning from INO. No methaemoglobin values >5% were reported during treatment. CONCLUSION: The overall mortality did not differ dramatically from historical controls with high mortality. Only a randomised study may determine whether INO as an adjunct to treatment alters the outcome in severe ALI. One cannot at present advocate the routine use of INO in patients with ALI outside such studies.

Response to nitric oxide inhalation in early acute lung injury.

OBJECTIVE: To evaluate the dose response of inhaled nitric oxide (NO) on gas exchange and central haemodynamics in patients with early acute lung injury (ALI). DESIGN: Prospective, multicentre clinical study. SETTING: General ICUs in university and regional hospitals. PATIENTS: 18 Patients with early ALI according to specified criteria. INTERVENTIONS: During controlled ventilation an inhalation system was used to deliver NO (1000 ppm in N2) and O2/air to the low pressure fresh gas inlet of a Siemens 900C ventilator. Haemodynamics and pulmonary gas exchange variables were measured at baseline and at stepwise increased inspiratory NO concentrations of 0.1, 0.3, 1, 3, 10, 30 and 100 ppm, each dose being maintained for 15 min. Dose testing was repeated the next day, and the response to prolonged (2 h) NO inhalation at 1 and 10 ppm was also tested. MEASUREMENTS AND RESULTS: Inhalation of NO produced a significant increase in PaO2 (P < 0.0025). The degree of response, as well as the optimal NO dose varied in individual patients and between different days. Venous admixture (QVA/QT) was reduced (P < 0.02) from 38% (31-46%) to 33% (26-41%). In our patients with early acute lung injury and only a moderate elevation in pulmonary arterial pressure NO inhalation did not reduce mean pulmonary artery pressure significantly, being 27.0 (21-30) mmHg at baseline and 26.0 (21-30) mm Hg at 100 ppm. CONCLUSIONS: This study shows that improvements in arterial oxygenation in response to inhaled NO may show great inter- as well as intraindividual variability, and that improvements in arterial oxygenation occur without any measurable lowering of the pulmonary artery pressure.

Islet amyloid polypeptide is expressed in endocrine cells of the gastric mucosa in the rat and mouse.

BACKGROUND/AIMS: Islet amyloid polypeptide (IAPP) or amylin is a novel islet hormone candidate with a suggested role in the regulation of glucose homeostasis and the pathogenesis of non-insulin dependent diabetes mellitus. Occurrence of IAPP in the gastrointestinal tract of rats and humans has also been shown. The expression of IAPP in the stomach of the rat and mouse and the possible colocalization of IAPP and known gastric hormones were investigated in this study. METHODS: In situ hybridization, immunofluorescence, and combined in situ hybridization and immunocytochemistry were used. RESULTS: IAPP messenger RNA and IAPP-like immunoreactivity were shown in the same endocrine cells in the antrum and fundus of the rat and in the antrum of the mouse. IAPP was expressed in a major population of somatostatin-immunoreactive cells as well as in small populations of gastrin- and peptide YY-immunoreactive cells. CONCLUSIONS: Our results establish the synthesis and storage of IAPP in gastric endocrine cells in the rat and mouse. The extensive colocalization of IAPP with somatostatin and to a lesser extent with gastrin and peptide YY suggests that IAPP may modulate endocrine activity in the gastric mucosa in a paracrine and/or autocrine mode.

Islet amyloid polypeptide gene expression in the endocrine pancreas of the rat: a combined in situ hybridization and immunocytochemical study.

The expression of the islet amyloid polypeptide (IAPP) gene within the endocrine pancreas and its correlation with insular neuroendocrine peptide localization were investigated in the rat. In situ hybridization with a 35S-labelled IAPP-mRNA specific oligonucleotide probe was combined with immunocytochemistry. In situ hybridization alone showed strong autoradiographic labelling of the pancreatic islets. In situ hybridization combined with immunocytochemistry for IAPP, revealed labelling of the IAPP-immunoreactive cells. However, when in situ hybridization was combined with immunocytochemistry for proinsulin, we noted a lack of proinsulin immunoreactivity in some peripherally located autoradiographically labelled islet cells. Furthermore, combination of in situ hybridization and immunocytochemistry for somatostatin showed autoradiographic labelling of somatostatin cells to a varying degree. This was further confirmed by showing cellular co-localization of IAPP and somatostatin by immunocytochemical double staining. We conclude that IAPP is mainly synthesized in insulin cells. Additionally, a subpopulation of the somatostatin cells is capable of IAPP synthesis. This may account for the relatively small reduction in the content of IAPP-mRNA in islets compared to the marked reduction of insulin mRNA after streptozotocin-induced diabetes in rats as previously reported.

Improved antihypertensive efficacy of the felodipine-metoprolol extended-release tablet compared with each drug alone.

In this double-blind, randomised, three-way crossover (latin square design), multicentre study, the aim was to compare the efficacy and tolerability of the fixed combination of felodipine and metoprolol with the individual components as monotherapy. A total of 58 patients with supine diastolic blood pressure of 100-115 mmHg were treated with (1) a fixed combination of felodipine plus metoprolol 5/50-10/100 mg (FM), (2) felodipine 5-10 mg (F) or (3) metoprolol 50-100 mg (M), for 12 weeks each. All treatments were extended-release formulations administered once daily and blood pressure was measured 24 h after dosing. Dose titration was performed after 6 weeks if diastolic blood pressure was > 90 mmHg. After 12 weeks of active treatment, the mean supine blood pressures were 153/89, 159/93 and 163/94 mmHg with FM, F and M, respectively. The mean differences in systolic/diastolic blood pressure were -5.6/-3.1 mmHg (p = 0.007/p = 0.002), -10.2/-4.4 mmHg (p < 0.0001/p < 0.0001) and -4.6/-1.4 mmHg (p = 0.03/p = 0.15) for FM vs F, FM vs M, and F vs M, respectively. Blood pressure control (supine diastolic blood pressure < or = 90 mmHg) after 12 weeks was achieved in a significantly greater proportion of patients during treatment with FM than with F or M; 71%, 45% and 40% were controlled with the respective treatments. With FM, 45% of the patients were taking the higher dose after 12 weeks of treatment. The corresponding figures for F and M were 60% and 67%, respectively. Thirteen of the 58 patients (22%) were controlled only with FM.(ABSTRACT TRUNCATED AT 250 WORDS)