Femoral impaction bone grafting with the Exeter stem - the Swedish experience: survivorship analysis of 1305 revisions performed between 1989 and 2002.

We identified 1305 femoral impaction bone grafting revisions using the Exeter stem performed between 1989 and 2002 in 30 hospitals throughout Sweden. There were 1188 patients with a mean age of 71 years (29 to 94) followed up for between five and 18 years. The participating departments reported 70 further revisions in total, of which 57 could also be identified on the Swedish National Arthroplasty Registry. Kaplan-Meier survivorship for all causes of failure was 94.0% (95% confidence interval (CI) 92 to 96) for women and 94.7% (95% CI, 92 to 96) for men at 15 years. Survivorship at 15 years for aseptic loosening was 99.1% (95% CI 98.4 to 99.5), for infection 98.6% (95% CI 97.6 to 99.2), for subsidence 99.0% (95% CI 98.2 to 99.4) and for fracture 98.7% (95% CI 97.9 to 99.2) Statistically significant predictors of failure were the year in which revision was conducted (p < 0.001). The number of previous revisions was slightly above the level of significance (p = 0.056). Age, gender, the length of the stem and previous septic loosening were not predictors of failure (p = 0.213, p = 0.399, p = 0.337, p = 0.687, respectively). The difference in survivorship between high- and low-volume departments was only 3% at ten years. We conclude that impaction bone grafting with the Exeter stem has an excellent long-term survivorship following revision arthroplasty. The technique of impaction grafting appears to be reliable, can be learned rapidly and produces a predictably low incidence of aseptic loosening.

A trabecular metal tibial component in total knee replacement in patients younger than 60 years: a two-year radiostereophotogrammetric analysis.

We compared the performance of uncemented trabecular metal tibial components in total knee replacement with that of cemented tibial components in patients younger than 60 years over two years using radiostereophotogrammetric analysis (RSA). A total of 22 consecutive patients (mean age 53 years, 33 to 59, 26 knees) received an uncemented NexGen trabecular metal cruciate-retaining monobloc tibial component and 19 (mean 53 years, 44 to 59, 21 knees) a cemented NexGen Option cruciate-retaining modular tibial component. All the trabecular metal components migrated during the initial three months and then stabilised. The exception was external rotation, which did not stabilise until 12 months. Unlike conventional metal-backed implants which displayed a tilting migration comprising subsidence and lift-off from the tibial tray, most of the trabecular metal components showed subsidence only, probably due to the elasticity of the implant. This pattern of subsidence is regarded as being beneficial for uncemented fixation.

Effect of low doses of 5-methyltetrahydrofolate and folic acid on plasma homocysteine in healthy subjects with or without the 677C-->T polymorphism of methylenetetrahydrofolate reductase.

BACKGROUND: The 677C-->T polymorphism of methylenetetrahydrofolate reductase can lead to increased homocysteine. Moderate increases of homocysteine can be lowered by folic acid (0.4-10 mg day-1). This study compared the effect of folic acid with 5-methyltetrahydrofolate, the active form of folate generated by this reductase, on homocysteine levels in healthy subjects and whether this is influenced by the 677C-->T polymorphism. MATERIALS AND METHODS: Either 400 micrograms day-1 of [6RS] 5-methyltetrahydrofolate or 400 micrograms day-1 of folic acid were administered orally to 10 wild-type and 10 homozygous subjects. Total homocysteine and folate were determined before and after 3 and 7 weeks of treatment, and 24 weeks after stopping treatment. RESULTS: After 3 and 7 weeks of treatment with 5-methyltetrahydrofolate, homocysteine levels fell from 11.6 +/- 1.5 to 9.0 +/- 2.3 and 8.7 +/- 1.8 (P < 0.005) in wild-type subjects and from 16.9 +/- 6.8 to 12.3 +/- 4.3 and 11.6 +/- 4.4 mumol/L, mean +/- SD (P < 0.005) in homozygous subjects, proving biological availability of 5-methyltetrahydrofolate irrespective of the 677C-->T genotype. After folic acid for 3 and 7 weeks, values fell from 12.6 +/- 3.3 to 9.2 +/- 2.9 and 9.2 +/- 2.7 (P < 0.005) and from 15.6 +/- 4.9 to 11.7 +/- 3.9 and 9.1 +/- 2.4 mumol L-1, mean +/- SD (P < 0.005) in wild-type and homozygous subjects, respectively. Six months after stopping treatment, homocysteine levels remained lower than pretreatment levels, with statistical significance, only in homozygous subjects treated with 5-methyltetrahydrofolate (12.1 +/- 2.5 vs. 16.9 +/- 6.8, P < 0.01). CONCLUSIONS: 5-methyltetrahydrofolate showed comparable efficacy in reducing homocysteine as folic acid. A prolonged effect 6 months after ceasing treatment with 5-methyltetrahydrofolate in homozygous subjects represents a further phenotypic effect of the 677TT methylenetetrahydrofolate reductase genotype.

[Infection a dreaded central venous catheter-related complication. A reminder of the significance of good aseptics is justified]. / Infektion en fruktad komplikation till användning av central venkateter. Motiverat att påminna om vikten av god aseptik.

The use of central venous catheters has increased markedly. Large numbers of patients are therefore at risk for catheter-related infections. This paper reviews the literature on prevention of intravascular catheter-related complications. Microbes colonising the catheter hubs and the skin around the insertion site are the source of most of these infections. By simple routines it is possible to reduce the risk for microbial spread from these sites to the bloodstream.

Effect of fluoride on glucose incorporation and metabolism in biofilm cells of Streptococcus mutans.

The aim of this study was two-fold: firstly, to study the effect of high fluoride concentrations on carbohydrate metabolism in Streptococcus mutans present in biofilms on hydroxyapatite; and, secondly, to evaluate the effect of fluoride-bound hydroxyapatite on lactic acid formation in growing biofilms of Strep. mutans. Biofilms of a clinical strain of Strep. mutans on saliva-coated hydroxyapatite beads were incubated with sodium fluoride over a wide range of concentrations. At high fluoride concentrations (>10 mM) the incorporation of [14C]-labeled glucose decreased by 80-85%, at both pH 7.0 and 5.6. At lower fluoride concentrations, the effect of fluoride on the incorporation of labeled glucose was pH-dependent in both biofilm cells and in planktonic cells. At pH 7.0, fluoride at concentrations < 10 mM had little or no effect. Pretreatment of hydroxyapatite discs with fluoride varnish (Fluor Protector) or fluoride solutions caused a statistically significant reduction of lactic acid formation in associated, growing biofilms of Strep. mutans. Fluoride varnish and 0.2% (47.6 mM) sodium fluoride solution exhibited a statistically significant inhibitory effect on lactate production.

Smoking and subgingival microflora in periodontal disease.

AIM: The present investigation was undertaken to analyze the influence of smoking on the periodontal disease associated subgingival microflora. The population included 33 smokers and 31 non-smokers in the age range 36-86 years. METHODS: Microbial samples were obtained from 4 sites per patient. The checker-board DNA-DNA hybridization technology was used for detection of the bacterial species P. gingivalis, P. intermedia, P. nigrescens, B. forsythus, A. actinomycetemcomitans, F. nucleatum, T. denticola, P. micros, C. rectus, E. corrodens, S. noxia and S. intermedius. RESULTS: Using score 1 as cutoff, contrasting colonized versus non-colonized patients, 8 out of 12 species were detected in > or = 90% of both smokers and non-smokers. Using score 4 as cutoff, contrasting heavily colonized patients versus non-colonized and less heavily colonized patients, the detection rates decreased in both smokers and non-smokers. No significant differences in detection rates were observed between smokers and non-smokers. Logistic regression analysis indicated that neither smoking, probing depth nor gingival bleeding influenced the occurrence of the species analyzed. The lack of a smoking exposure dose-response further supported the indication of a limited influence of smoking. CONCLUSION: Smoking exerts little, if any, influence on the subgingival occurrence of several of the bacteria most commonly associated with periodontal disease.

Measurement of immunoreactive angiotensin-(1-7) heptapeptide in human blood.

BACKGROUND: The renal enzyme renin cleaves from the hepatic alpha(2)-globulin angiotensinogen angiotensin-(1-10) decapeptide [Ang-(1-10)], which is further metabolized to smaller peptides that help maintain cardiovascular homeostasis. The Ang-(1-7) heptapeptide has been reported to have several physiological effects, including natriuresis, diuresis, vasodilation, and release of vasopressin and prostaglandins. METHODS: To investigate Ang-(1-7) in clinical settings, we developed a method to measure immunoreactive (ir-) Ang-(1-7) in 2 mL of human blood and to estimate plasma concentrations by correcting for the hematocrit. A sensitive and specific antiserum against Ang-(1-7) was raised in a rabbit. Human blood was collected in the presence of an inhibitor mixture including a renin inhibitor to prevent peptide generation in vitro. Ang-(1-7) was extracted into ethanol and purified on phenylsilylsilica. The peptide was quantified by radioimmunoassay. Increasing doses of Ang-(1-7) were infused into volunteers, and plasma concentrations of the peptide were measured. RESULTS: The detection limit for plasma ir-Ang-(1-7) was 1 pmol/L. CVs for high and low blood concentrations were 4% and 20%, respectively, and between-assay CVs were 8% and 13%, respectively. Reference values for human plasma concentrations of ir-Ang-(1-7) were 1.0-9.5 pmol/L (median, 4.7 pmol/L) and increased linearly during infusion of increasing doses of Ang-(1-7). CONCLUSIONS: Reliable measurement of plasma ir-Ang-(1-7) is achieved with efficient inhibition of enzymes that generate or metabolize Ang-(1-7) after blood sampling, extraction in ethanol, and purification on phenylsilylsilica, and by use of a specific antiserum.

Local effect of transdermal isosorbide dinitrate ointment on hand vein diameter.

OBJECTIVE: To assess the effect of topically applied isosorbide dinitrate (ISDN) ointment on superficial hand veins preconstricted with phenylephrine. METHODS: Using the hand vein compliance technique, venous diameter changes were measured in a double-blind, randomised, placebo-controlled cross-over trial in 12 healthy volunteers. During preconstriction with phenylephrine, placebo or ISDN ointment was administered to assess the dilator effect of transdermal ISDN. Finally a single i.v. dose of nitroglycerine was administered into the hand vein to assess the maximal venous response to organic nitrovasodilators. RESULTS: ISDN ointment (equivalent to 13.4 +/- 3.61 mg ISDN) caused a significant dilator effect of 39.1 +/- 21.7% (mean +/- SEM, P=0.02) which reached its maximum after 42.5 +/- 16.6 min. Maximum ISDN effects were inversely correlated with venous baseline diameter (r2=0.38, P=0.03) and independent of the amount of ointment applied or the extent of preconstriction (P > 0.3). CONCLUSION: Similar to nitroglycerine, topical ISDN may relax superficial hand veins within 60 min after application, suggesting that it might ease venepuncture particularly of small vessels. The large variability of the effect and the time to reach the effect, however, restrict its practical usefulness.

Tumor necrosis factor-alpha and transforming growth factor-beta1 in chronic periapical lesions.

OBJECTIVE: Proinflammatory cytokines are involved in the pathogenesis of periapical lesions. The purpose of this study was to evaluate the presence of the cytokines tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(1) (TGF-beta(1)) in periapical pathosis and to determine their relationship to the size of the lesions. STUDY DESIGN: One tooth from each of 25 patients was root-end resected, and the periapical lesion was collected. The amounts of TNF-alpha and TGF-beta(1) were assessed by enzyme-linked immunosorbent assay. RESULTS: TGF-beta(1) was detected in 21 of 25 lesions. In samples with scar tissue, no TGF-beta(1) activity was detected. A statistically significant correlation was found between TGF-beta(1) per milligram of tissue and the diameter of the lesions. TNF-alpha was detected in only 2 samples. CONCLUSIONS: TGF-beta(1) was present in periapical granulomas and cysts but not in lesions with scar tissue. The correlation between the amount of TGF-beta(1) per milligram of tissue and the size of the lesion was significant.

Correlation between apolipoprotein B and endothelin-1-induced vasoconstriction in humans.

Low-density lipoprotein (LDL) concentrations have been linked to altered responses to endogenous vasodilators and vasoconstrictors. We evaluated retrospectively the relationship between LDL and vasoconstrictor (endothelin-1, phenylephrine) responsiveness of the forearm vasculature in 15 elderly healthy volunteers with apolipoprotein B and LDL levels in the normal range. In contrast to phenylephrine, changes in forearm vascular resistance induced by endothelin-1 were correlated with apolipoprotein B, LDL, and total cholesterol concentrations in women but not in men. These findings might suggest that lipids may increase vascular tone through both impaired endothelial vasodilation and increased vasoconstriction to endothelin-1 at least in women.

Smoking and GCF levels of IL-1beta and IL-1ra in periodontal disease.

AIMS: GCF levels of the cytokine IL-1beta and its receptor antagonist IL-1ra were analyzed with respect to smoking in patients with moderate to severe periodontal disease. The study population included 22 smokers and 18 non-smokers in the age range 32-86 years. Concomitantly, the GCF levels of IgA, IgG, albumin and total protein were analyzed. METHOD: Samples of GCF were obtained from 2 diseased sites in each patient by means of an aspiration method. IL-1beta, IL-1ra, IgA and IgG were determined with immunoelectrophoresis. Total protein was determined by the BCA method. RESULTS: The clinical characteristics in terms of probing depth and frequency of diseased sites and supragingival plaque did not differ between smokers and non-smokers. Gingival bleeding, however, was significantly depressed in smokers. IL-1beta was detected in GCF of 95% of both smokers and non-smokers and IL-1ra in all patients. The GCF level of IL-1ra was approximately 1,000-fold that of IL-1beta. The GCF levels of IL-1beta and IL-1ra were high in comparison with those of TNF-alpha and IL-6 determined by the same method in our earlier studies. CONCLUSION: Our observations did not reveal any influence of smoking on the levels of IL-1beta and IL-1ra in GCF.

Effect of four dental varnishes on the colonization of cariogenic bacteria on exposed sound root surfaces.

The aim of this study was to evaluate the effect of four different dental varnishes on the colonization of mutans streptococci, total streptococci and lactobacilli on exposed sound root surfaces. Sixty-five individuals were randomly allotted to one of four groups for treatment with Cervitec((R) ) varnish containing 1% chlorhexidine and 1% thymol, a thymol varnish or one of two different fluoride varnishes, Fluor Protector and Duraphat. The varnish was applied to three buccal root surfaces in each patient at baseline and after 1 week. Dental plaque from the root surfaces was collected and analysed on four different occasions: at baseline, after 1 week, 1 month and 6 months. The Cervitec varnish caused a statistically significant reduction in the number of mutans streptococci over time. The reduction was significant at 1 week and 1 month relative to baseline. The numbers of total streptococci and lactobacilli were not significantly affected by treatment with Cervitec. No statistically significant difference over time was found for mutans streptococci, lactobacilli or total streptococci after treatment with the fluoride varnishes or the thymol varnish.

Auditory and electroencephalographic effects of midazolam and alpha-hydroxy-midazolam in healthy subjects.

AIMS: Whereas cortical EEG effects of benzodiazepines are well characterized, information about benzodiazepine effects in other areas of the central nervous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the auditory pathway in six healthy volunteers in a randomized, double-blind, three-way cross-over study. METHODS: Acoustically evoked short (SLP) and middle (MLP) latency potentials, transitory evoked otoacoustic emissions (TEOAE), and EEG power spectra were analysed after short i. v. injections of placebo, or 0.15 mg kg-1 midazolam, or alpha-hydroxy-midazolam, respectively. RESULTS: All subjects fell asleep during the 4 min infusion of active drug. SLP showed a significant transient increase of Jewett wave V 10 min after injection for midazolam and alpha-hydroxy-midazolam while the latency of wave I was unchanged. Both benzodiazepines induced a marked and long-lasting MLP amplitude decrease for 240 min with slow recovery over the following 360 min. No changes of TEOAE were observed. In agreement with earlier reports, increases in EEG beta activity and decreases in alpha activity were observed after administration of either drug. CONCLUSIONS: Systemically administered benzodiazepines modulate the auditory pathway above the level of the cochlea. While SLP changes were closely associated with sedation and high plasma benzodiazepine concentrations, MLP effects persisted for hours after sedation even at low benzodiazepine plasma levels. Evoked potentials may therefore be more sensitive than EEG as a tool to monitor benzodiazepine effects.

Cancellous impaction grafting in the human femur: histological and radiographic observations in 6 autopsy femurs and 8 biopsies.

6 whole postmortem femurs and 8 femoral biopsies were studied histologically, 3 months to 8 years after cancellous impaction grafting with a cemented stem for aseptic loosening. All stems were stable. Radiographs showed cortical healing in 5 cases, trabecular remodelling in 1, and trabecular incorporation in 9. There was a radiolucent line in 1 case. The histology varied. There was always a viable cortical shell around the grafted area. 1 patient showed complete bony restitution. The others still had varying amounts of remaining graft in the neo-medullary cavity, even after 8 years. The graft particles were usually embedded in dense fibrous tissue, thus forming a supporting composite tissue capable of carrying load. There was no time-dependent deterioration in the histological appearance. Radiographically, cortical healing and trabecular remodeling corresponded to viable bone. The lack of a radiolucent line said little about the viability of the tissue closest to the cement. The radiographs did not detect thin soft tissue membranes. Radiographic criteria used to assess primary total joint replacement do not necessarily apply to impaction grafting, and radiographic changes should be interpreted cautiously, especially as regards tissue viability.

Neurokinin-1 receptor antagonist R116301 inhibits substance P-induced venodilation.

OBJECTIVE: To test the effect of the neurokinin-1 receptor antagonist hydroxybutanedioate (R116301) in human hand veins in vivo. METHODS: In a randomized, double-blind, placebo-controlled crossover study we used the hand vein compliance method to evaluate the inhibition of the response to substance P by R116301. RESULTS: In hand veins preconstricted with phenylephrine to 21% +/- 2.6% (mean +/- SEM, placebo) and 25% +/- 3.0% (R116301) of the initial diameter, substance P resulted in a mean venodilation of 84% +/- 7% and 87% +/- 13% (P = .8) before administration of placebo and R116301, respectively. Oral administration of 300 mg R116301 resulted in peak plasma concentrations of 1.16 +/- 0.1 microg/mL within 128 +/- 14 minutes. With increasing R116301 plasma concentrations, substance P-induced venodilation decreased significantly (P < .001), whereas placebo had no effect. Mean substance P-induced venodilation was markedly reduced to 8% +/- 7%. CONCLUSION: This study confirms the presence of neurokinin-1 receptors in human veins and the effectiveness of the neurokinin-1 receptor antagonist R116301 in human hand veins.

Pharmacokinetics and pharmacodynamics of clomethiazole after oral and rectal administration in healthy subjects.

Clomethiazole, a sedative-hypnotic and anticonvulsant drug, has been successfully administered orally and intravenously, but in cases where either of these methods presents complications, rectal administration may represent a practical alternative. We sought to compare the single-dose pharmacokinetics and pharmacodynamics of clomethiazole after oral and rectal administration. Ten healthy adult volunteers were given 600 mg clomethiazole edisylate (corresponding to 390 mg clomethiazole base) in 2 capsules as a single oral or rectal dose in a double-masked, double-dummy, crossover fashion. Serum concentrations were measured up to 10 hours after administration using a specific high-performance liquid chromatography method. Computerized reaction-time measurement and visual analogue scales (VAS) were used to assess drug effects. Peak serum concentrations were significantly higher after oral administration (mean +/- SEM, oral 1.76 +/- 0.47 microg/mL vs rectal 0.48 +/- 0.14 microg/mL; P = 0.03) and appeared earlier (55 +/- 12 vs 89 +/- 11 min; P = 0.04). Area under the concentration-time curve values were similar after administration by both routes (oral 116 +/- 20.6 vs rectal 105 +/- 36.0 microg x min/mL), with a relative rectal bioavailability of 90% compared with oral administration. The objective pharmacodynamic effects on reaction time (increase of 104 +/- 26 vs 66 +/- 22 ms, oral vs rectal) and working speed (decrease of 132 +/- 38 vs 97 +/- 32 ms, oral vs rectal) were not significantly different. Subjective pharmacodynamic effects, as measured on the VAS, were comparable with both routes of administration. Clomethiazole was well tolerated, with a similar adverse effect profile for both routes of administration. The effects of rectal dosing of clomethiazole were similar to those of oral dosing but appeared to occur later. Our results suggest that rectal administration of a single 600-mg clomethiazole edisylate dose bears no safety risk. Therefore, rectal administration could be considered when neither oral nor parenteral administration is possible and a later onset of effect is not critical.

Smoking and crevicular fluid levels of IL-6 and TNF-alpha in periodontal disease.

Smoking is a well-documented risk factor for periodontal disease, although the mechanisms of its negative influence are not well understood. In the present study, the influence of smoking on the gingival crevicular fluid (GCF) content of the pro-inflammatory cytokines IL-6 and TNF-alpha was investigated in patients with moderate to severe forms of the disease. The study base consisted of 108 patients including 45 current smokers, 28 former smokers and 35 non-smokers. The median GCF sample levels of IL-6 and TNF-alpha were 5.0 pg/ml and 61.0 pg/ml, respectively, for current smokers, 13.0 pg/ml and 51.0 pg/ml, respectively, for former smokers, and 10.0 pg/ml and 12.0 pg/ml, respectively, for non-smokers. The differences between smoking groups with regard to IL-6 were not significant suggesting that the IL-6 content was not influenced by smoking. In contrast, the TNF-alpha content was significantly increased in current smokers as compared to non-smokers confirming our previous observations. The present results in patients with moderate to severe periodontal disease may indicate different mediator functions of IL-6 and TNF-alpha in response to smoking.

Outcomes of periradicular surgery in cases with apical pathosis and untreated canals.

OBJECTIVE: Surgical management is intended to eliminate or block infection originating in the root canals. The root end is customarily sealed to prevent pathogenic products remaining in the root canal from reaching the periradicular tissues. The purpose of this study was to evaluate the microbiologic and radiographic outcomes of surgical treatment of periradicular pathosis associated with teeth with necrotic pulps. STUDY DESIGN: One tooth from each of 10 patients was root-end resected and root-end filled without prior root canal treatment. One year postoperatively, the outcomes were assessed radiographically and the root canals were sampled for bacteria. RESULTS: Radiographic examination showed complete or incomplete (scar tissue) healing in 5 teeth and uncertain healing in the other 5 teeth. Bacteriologic samples from the root canals were positive in 9 of the 10 cases. CONCLUSIONS: In teeth with necrotic pulps, treatment of periradicular pathosis by surgery and root-end filling may show radiographic evidence of satisfactory healing 1 year postoperatively. However, viable bacteria may persist in the canals, constituting a potential risk factor for recurrence of periradicular pathosis.

Clinical expression of TNF-alpha in smoking-associated periodontal disease.

The level of TNF-alpha in gingival crevicular fluid (GCF) was analyzed with respect to smoking in patients with untreated moderate to severe periodontal disease including 30 current smokers, 19 former smokers and 29 non-smokers, in the age range 31-79 years. Concomitantly the occurrence of the periopathogens Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Prevotella intermedia (Pi) and the GCF levels of albumin, IgA and IgG were analyzed. With regard to clinical characteristics, there were no statistically significant differences between smoking groups. The occurrence of patients positive for the periopathogens Aa, Pg and Pi was 28.2%, 41.0% and 91.0%, respectively. There were no statistically significant differences between smoking groups with regard to occurrence or relative frequency of these periopathogens. An exception was a significantly lower occurrence of Aa in former smokers as compared to non-smokers. The chief novelty of the study was the observation of a clearly increased level of TNF-alpha in GCF associated with smoking. Both current and former smokers exhibited significantly higher levels of TNF-alpha in comparison to non-smokers, whereas the levels of albumin, IgA and IgG were the same irrespective of smoking. In conclusion, the present observations in patients with moderate to severe periodontal disease suggest that smoking is associated with elevated GCF levels of the cytokine TNF-alpha.

Human neuropeptide Y potentiates alpha1-adrenergic blood pressure responses in vivo.

Human neuropeptide Y (hNPY) potentiates the postjunctional vasoconstrictor effects of alpha1-adrenoceptor agonists in animals and in human hand veins in vivo. We therefore hypothesized that such an interaction might also occur in the human arterial bed. With the present single-blind cross-over study in 12 healthy volunteers, the effect of subpressor doses of hNPY on the blood pressure response to alpha1-adrenoceptor stimulation was evaluated. Dose-response curves were constructed to intravenously infuse phenylephrine with and without coinfusion with two different doses of hNPY (1.4 and 14.3 pmol . kg-1 . min-1). Blood pressure, heart rate, and forearm blood flow were recorded, and plasma hNPY was determined. During infusion of the higher hNPY dose, which increased hNPY from 24.0 +/- 12.0 to 495.1 +/- 12.6 pmol/l, blood pressure curves were 2.4-fold shifted toward lower phenylephrine dose rates (P < 0.001). Forearm vascular resistance showed a similar trend, whereas the counterregulatory decrease of heart rate was similar in both groups. In contrast, the lower hNPY dose rate producing a fourfold increase in hNPY concentrations did not modify the response to phenylephrine. This in vivo study in humans demonstrates that hNPY induced potentiating effects on alpha1-adrenergic constriction also in the systemic arterial circulation and suggests that circulating hNPY may participate in the control of vascular tone.