Assessment of Progression and Treatment Response of Optic Pathway Glioma with Positron Emission Tomography using α-[<Superscript>11</Superscript>C]Methyl-<Emphasis Type="SmallCaps">l</Emphasis>-Tryptophan

Purpose To report the utility of positron emission tomography (PET) with α-[¹¹C]methyl-l-tryptophan (AMT) for monitoring progression and response to treatment of an isolated optic pathway glioma (OPG) in a 16-year-old girl. Procedures Positron emission tomography scanning of the brain was performed 20 minutes after intravenous administration of AMT. The AMT-PET images were reconstructed and examined for tumor uptake of the tracer in correlation with coregistered magnetic resonance images. Results The PET scan demonstrated increased uptake of AMT by OPG in a clinically symptomatic child whose magnetic resonance imaging (MRI) was inconclusive for morphological changes of the tumor. The tracer uptake was dramatically decreased on the images obtained after chemotherapy. Subsequently, AMT-PET revealed a new tumor lesion of increased AMT uptake when the patient developed vision problems and MRI showed no significant interval morphological changes. Significant vision improvement was observed after external beam radiotherapy for the newly identified tumor lesion. Conclusions Positron emission tomography with α-[¹¹C]methyl-l-tryptophan may be useful for monitoring progression and response to treatment of OPGs, which needs to be further investigated in a prospective study of more patients, including those with neurofibromatosis.     

(1→3)-β-d-glucan determination in rat organs with limulus coagulation factor G

One cause of a false positive limulus test after surgery or hemodialysis has been identified as extrinsic (1→3)-β-d-glucan which was derived from surgical gauze or cellulose dialyzer. However, there have been no investigations concerning intrinsic factors and the presence of (1→3)-β-d-glucan in mammalian organs. In this study, (1→3)-β-d-glucan in homogenate of various rat organs and stool was measured by a Gluspecy test (G test) using factor G, which specifically reacts with (1→3)-β-d-glucan. In small intestine and lung, large amounts of factor G-activating substance were observed and identified as (1→3)-β-d-glucan by a digestion study using end-(1→3)-β-d-glucanase. However, only very small amounts of (1→3)-β-d-glucan were found in the kidney, spleen, vena cava, aorta, thymus, heart and liver. In serum and plasma, no (1→3)-β-d-glucan was observed. On the other hand, extremely large amounts of (1→3)-β-d-glucan were found in stool. Minute amounts of (1→3)-β-d-glucan were observed in a variety organs except for the small intestine and lung. High levels of (1→3)-β-d-glucan found in the small intestine might be traced to contamination by stool in the small intestine, and such levels in the lung might derive from macrophages which have trapped (1→3)-β-d-glucan in the air.     

Asparaginase decreases clotting factors in vitro: a possible pitfall?

Summary l-Asparaginase treatment of leukemia patients causes hemostatic problems. To investigate whetherl-asparaginase influences coagulation studies, 63 blood samples of 21 healthy male donors were incubated withl-asparaginase for 30 min at room temperature. After treatment with 100 IU/mll-asparaginase plasma fibrinogen (P=0.002), plasma antithrombin (P=0.0002), plasma protein C (P=0.0004), and plasma plasminogen (P=0.0039) were decreased compared with controls. In contrast, a significant increase in plasma von Willebrand factor antigen (P=0.08) and plasma thromboglobulin (P=0.005) was observed. The decrease in plasma antithrombin (P=0.001), plasma protein C (P=0.0003), and plasma plasminogen (P=0.0043) was also measurable after 0.05 IU/ml asparaginase treatment. The incubation withl-asparaginase was similar to the normal time from blood sampling to testing and hence the results suggest thatl-asparaginase may directly attack proteins of the coagulation system during the interval between sampling and assay.     

Concentrations ofd-lactate and its related metabolic intermediates in liver,blood, and muscle of diabetic and starved rats

This is a report investigating the methylglyoxal (MG) bypass in animals, by whichd-lactate is produced from triosephosphate via MG. Rats were made diabetic using streptozotocin or starved for 72 h.d-Lactate and various metabolites related to it, such asl-lactate, pyruvate, methylglyoxal, glucose, and inorganic phosphate, were measured in the blood plasma, liver, and skeletal muscle of the rats. Diabetic and starved rats had significantly higher levels ofd-lactate in plasma, liver, and skeletal muscle compared with the control group. In contrast, pyruvate levels in plasma, liver, and skeletal muscle was markedly lower than normal in diabetic and starved rats.l-Lactate level lowered markedly in plasma, liver, and skeletal muscle of starved rats and elevated in liver of diabetic rats. Differences between plasmal-lactate level for diabetes and control were not significant. MG level was significantly elevated in plasma and depressed in livers and muscles of starved rats as well as livers of diabetic rats. Hepatic glycerol content was markedly increased in those states. Enzyme activities related tod- andl-lactate, such as pyruvate kinase, phosphofructokinase, aldolase, and glyoxalase I, were measured in the livers of these rats. Pyruvate kinase activity decreased in these states, but other enzyme activities showed no significant changes.d-Lactate was much more excreted thanl-lactate in the urine of diabetic and fasted rats compared with normal rats.     

Gastric PgCO2 and Pg-aCO2 gap are related to D-lactate and not to L-lactate levels in patients with septic shock

Objective Intestinal ischemia causes an increase in lactate production and gastric intramucosal carbon dioxide partial pressure (PgCO₂). However, no linear relationship between systemic l-lactate levels and gastric tonometry during intestinal ischemia has been found, probably since l-lactate is rapidly cleared from the circulation by the liver. In contrast, the rate of d-lactate clearance from the circulation by the liver is considerably lower than that of l-lactate, and d-lactate may therefore be more closely related to measurements of gastric tonometry than l-lactate values.Design and setting Prospective, observational study in a university-affiliated mixed intensive care unit.Subjects Twenty critically ill patients with septic shock.Measurements and results During the first 24 h of admission to the intensive care unit at least two blood samples were taken for d- and l-lactate measurements and arterial blood gases, Simultaneously, gastric PgCO₂ was measured using capnographic tonometry. The intramucosal-arterial PCO₂ gap was calculated using gastric intramucosal PgCO₂ and arterial PCO₂ from arterial blood. d-Lactate was significantly correlated to PgCO₂ values and to the mucosal-arterial PCO₂ gap. There was no relationship between l-lactate and PgCO₂ or the mucosal-arterial PCO₂ gap. d-lactate and l-lactate values were significantly correlated.Conclusions During sepsis intestinal production of d-lactate is related to gastric intramucosal PCO₂. No such relationship was found between l-lactate values and PgCO₂     

Oxidative stress in lymphocytes,neutrophils, and serum of oral cavity cancer patients: modulatory array of <Emphasis Type="SmallCaps">l</Emphasis>-glutamine

Objectives Our aim was to assess the oxidative stress and ameliorative effect of l-glutamine in serum, neutrophils, and lymphocytes of oral cancer patients by measuring the levels of malondialdehyde (MDA) and antioxidants. Materials and methods This study has been conducted on serum and specific blood cells in adult, male oral cancer patients (stage III-6, stage IV-42) and normal subjects of an equal number of age and sex-matched disease-free healthy subjects. The levels of lipid peroxidation and antioxidant enzymes were assayed using spectrophotometric methods. Results MDA levels were elevated, and antioxidant enzyme status was decreased significantly in all groups of cancer patients simultaneously, but after supplementation of “glutammune” (66.66% l-glutamine), oxidative stress has been alleviated to some extent; especially, it has repaired the glutathione cascade system. Conclusion We conclude that oxidative stress is due to the enhanced lipid peroxidation and decrease in antioxidant enzymes, and it can be restored with dietary supplementation of l-glutamine related drug.     

Effect of interleukin-10 (IL-10) on experimental LPS-induced acute lung injury

The purpose of this study was to clarify the role of interleukin-10 (IL-10) during the development of acute lung injury induced by lipopolysaccharide (LPS) in a mouse model. When LPS was given to nude mice, the mortality rate was 100% at 48 h of the observation period. However, mortality was reduced to 30% when IL-10 was added concomitantly (P < 0.01). In the IL-10 group, a significant reduction of inflammatory change in lung tissue was observed. It was also found that peripheral neutrophils increased when IL-10 was added. When LPS and IL-10 were given concomitantly, the level of tumor necrosis factor (TNF)-α in both serum and bronchoalveolar lavage fluid (BALF) decreased significantly (P < 0.05). In-vitro observations were made concerning the influence of human neutrophils. Both neutrophil superoxide (O₂ ⁻) and elas-tase production were increased by TNF-α stimulation, while significant inhibition was seen with the concomitant dosing of IL-10 (P < 0.05). TNF-α stimulation increased the occurrence of adhesion molecules for neutrophil surface, lymphocyte function-associated antigen-1 (LFA-1), and macrophage antigen-1 (Mac-1). LPS stimulation greatly increased the occurrence of neutrophil surface 55-kDa TNF-receptor [TNF-R (p55)], when observation was made under laser microscopy. However, no significant occurrence was seen with IL-10 concomitant dosing. The above results suggested that IL-10 inhibited TNF-α production and neutrophil activity in LPS-induced acute lung injury, which led to a reduction of the lung tissue injury. Received: February 18, 1999 / Accepted: December 20, 1999     

l-Arginine therapy in Raynaud's phenomenon?

Summary Sincel-Arginine is the substrate for nitric oxide synthesis by vascular endothelial cells the effects ofl-arginine treatment on the digital vascular response to local stimuli were investigated in patients with primary or secondary Raynaud's phenomenon. After therapy, patients withu Raynaud's phenomenon secondary to systemic sclerosis showed: (1) higher digital vasodilation after local warming, (2) cold-induced digital vasodilation, and (3) increase of plasma levels of tissue-type plasminogen activator.     

Comparison ofl-hyoscyamine,glucagon, and placebo for air-contrast upper gastrointestinal series

Previous studies have compared the use of anticholinergic drugs and glucagon for upper gastrointestinal (UGI) radiography. Many radiologists prefer glucagon because these comparisons showed it to have a shorter duration of action with fewer side effects.l-Hyoscyamine is the levo-rotatory form of atropine with minor adverse side effects. This study compared the effects of glucagon (N=48),l-hyoscyamine (N=43), and placebo (N=45) on gastric and duodenal distension, mucosal coating, and patient tolerance.l-Hyoscyamine provided gastric and duodenal images equal in quality to glucagon. Except for the more frequent reporting of dry mouth withl-hyoscyamine, side effects were not different among the groups.l-Hyoscyamine is an economical alternative to glucagon for hypotonic gastrointestinal radiography.     

Effect of various agonists on nitric oxide generation by human polymorphonuclear leukocytes

Nitric oxide generation is involved in a range of diseases involving polymorphonuclear leukocytes. The aim of this study was to determine whether human polymorphonuclear leukocytes are able to generate nitric oxide and to investigate the time course of its generation after stimulation with 10⁻⁷ MN-formyl-methionyl-leucylphenylalanine, 60 ng/ml phorbol myristate acetate, 10⁻⁷ M concanavalin A, and 10⁻⁷ M platelet activating factor. Stimulation of human polymorphonuclear leukocytes withN-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate caused sustained nitric oxide generation, reaching maximal values of 1,105±361 nM (n=32) and 628±119 nM (n=30), respectively. Platelet activating factor did not affect nitric oxide production (maximal value 29±7 nM,n=8), whereas concanavalin A caused only a slight increase (102±24 nM,n=8) when compared with resting cells control (26±6 nM,n=8). Human polymorphonuclear leukocytes were able to respond to both consecutive and alternateN-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate stimulation with nitric oxide generation. Nitric oxide generation was inhibited by specific inhibitors (N ^ω-nitro-l-arginine andN ^ω-monomethyl-l-arginine) and restored withl-arginine. We provide, to our knowledge, the first direct evidence that human neutrophils generate nitric oxide.     

Increasing Uptake Time in FDG-PET: Standardized Uptake Values in Normal Tissues at 1 versus 3 h

Objective  Positron emission tomography (PET) imaging at more than 1 h after 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) administration may result in less blood pool activity and possibly decreased normal FDG uptake in tissues such as liver. Lower normal background activity could be an important component of improved image contrast on delayed imaging. Increasing FDG uptake in normal organs, however, may mitigate the beneficial effects of blood pool clearance. The purpose of this study is to determine the normal tissue and blood pool FDG uptake at 1 and 3 h after injection. Subjects and methods  Ninety-nine patients with known or suspected malignancy referred for FDG-PET–computed tomography (CT) were retrospectively evaluated. PET imaging was performed at either 1 h (60 ± 15 min; n = 50) or at 3 h (180 ± 15 min; n = 49) after FDG administration. Normal tissue FDG uptake without involvement by malignancy or influenced by artifact (misregistration, “brown fat,” focal muscle uptake, focal atherosclerotic disease) was confirmed by inspection of both the PET and CT scans. Aortic blood pool, adipose tissue, bone marrow, cerebellum, liver, lungs, muscle, and spleen were quantitatively evaluated by CT-guided region of interest analysis in three contiguous slices. Mean standardized uptake values (SUVs) were analyzed using one-way analysis of variance. Results  Mean SUVs on the 3- versus 1-h images were significantly lower for aortic blood pool 13% (p < 0.0001) and adipose tissue 20% (p < 0.008). FDG uptake showed significant increases at 3 h compared to 1-h imaging in the cerebellum 40% (p < 0.0001), bone marrow 25% (p = 0.003), muscle 21% (p = 0.0004), and spleen 13% (p = 0.01). The liver and lung showed no significant differences (1%, p = 0.85; −2%, p = 0.62, respectively). Conclusions  On FDG imaging at 3 h compared to 1 h, significant changes were apparent, but the magnitude of changes was modest overall. Three-hour delayed imaging demonstrated significantly lower aortic blood pool and adipose tissue activity and significantly higher cerebellum, muscle, spleen, and bone marrow activity. Hepatic and lung activities were not significantly different. These results suggest that previously reported improvements in tumor image contrast with delayed imaging may be primarily due to cumulative FDG uptake within the tumor rather than reduction in normal background activity.     

Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep

Objective: The present study compared the effects of nitric oxide (NO) synthase inhibition and NO scavenging with haemoglobin in endotoxaemic sheep. Design: 12 sheep were instrumented for chronic study. Six sheep received l ^G-nitro-arginine-methylester (l-NAME, 2.5 mg/kg bolus followed by a continuous infusion of 0.5 mg/kg per h), the other 6 sheep received pyridoxalated haemoglobin polyoxyethylene conjugate (PHP, 100 mg/kg bolus followed by a continuous infusion of 20 mg/kg per h). Measurements and results: Haemodynamic and oxygenation parameters were measured in healthy sheep, after infusion of Salmonella typhosa endotoxin (10 ng/kg per min) for 24 h and after infusion of l-NAME or PHP. The infusion of endotoxin resulted in a hypotensive, hyperdynamic circulation. Infusion of l-NAME increased mean arterial pressure (MAP) from 76.1 ± 4.2 mmHg to normal values of 95.8 ± 5.7 mmHg (p < 0.05). PHP increased MAP from 73.0 ± 3.0 to 88.6 ± 4.7 mmHg (p < 0.05). This increase in MAP was associated in the l-NAME group with a more prominent drop in cardiac index (from 10.2 ± 0.4 to 7.0 ± 0.5 l · min^–1· m^–2; p < 0.05) than in the PHP group (from 10.7 ± 0.2 to 9.3 ± 0.6 l · min^–1· m^–2). During the first 90 min of infusion, cardiac index remained lower in the l-NAME group than in the PHP group. The increase in pulmonary vascular resistance was also higher in the l-NAME group. Conclusion: These results suggest, that at the doses used in the experiment, NO scavenging with PHP has smaller effects on cardiac index and pulmonary vascular resistance than NO synthase inhibition with l-NAME. Therefore, the concept of NO scavenging in hyperdynamic sepsis should be further evaluated. Received: 29 January 1997 Accepted: 23 October 1997     

Adhesion preventive effect of a novel hyaluronic acid gel film in rats

This study evaluated the efficacy of a novel hyaluronic acid (HA) gel for preventing adhesions in a rat caecal model. The gel was manufactured from an acidic HA solution using a freezing procedure. HA gel films with four different half-lives (50-200 h) in physiological buffered saline at 37 degrees C were prepared, by regulating the freezing time, and tested. The HA gel film was applied as a barrier on the injured caecal surface after standardized treatment with a rotary abrasion apparatus. A control group of 20 animals were abraded in the same way but not treated. Seven days after the initial operation, the incidence and severity of any adhesions were recorded. Application of the HA gel film significantly reduced the incidence and severity of adhesion formation in all treatment groups compared with the control group. This novel HA gel film is effective for reducing post-operative adhesions in this rat model and the resorption rate is optimum for adhesion prevention on the caecal surface.     

<Superscript>11</Superscript>C-<Emphasis Type="SmallCaps">l</Emphasis>-Methionine Positron Emission Tomography in the Clinical Management of Cerebral Gliomas

Positron emission tomography (PET) using l-[methyl-¹¹C]-methionine (MET) is the most popular amino acid imaging modality in oncology, although its use is restricted to PET centers with an in-house cyclotron facility. This review focuses on the role of MET–PET in imaging of cerebral gliomas. The biological background of tumor imaging with methionine is discussed with particular emphasis on cellular amino acid transport, amino acid utilization in brain, normal metabolism of methionine, and its alterations in cancer. The role of MET–PET in clinical management of cerebral gliomas in initial diagnosis, differentiation of tumor recurrence from radiation injury, grading, prognostication, tumor-extent delineation, biopsy planning, surgical resection and radiotherapy planning, and assessment of response to therapy is also reviewed in detail.     

Pharmacokinetics and influence of arbekacin on renal function in low-birth-weight infants

Arbekacin (ABK) is an aminoglycoside with excellent antibacterial activity against methicillin-resistantStaphylococcus aureus (MRSA). Although ABK is expected to be a useful drug for MRSA infection in newborns, there have been few reports concerning its pharmacokinetics, efficacy, and safety. Ten low-birth-weight infants were treated with ABK. Their mean gestational age was 29.4±5.3 weeks and their mean birth weight was 1204±532 grams. At the time of initial ABK administration, the mean postconceptional age was 33.9±4.2 weeks. ABK was infused over a period of 30 minutes every 12 hours at doses ranging between 2.2 and 3.1 mg/kg. Trough (predose) and peak (30 minute postdose) serum ABK concentrations were determined. TheN-acetyl-β-d-glucosaminidase (NAG) index (NAG:creatinine ratio) was measured before and after ABK therapy. The mean peak serum ABK concentration was 8.49±2.06 μg/mL and the mean trough concentration was 3.93±2.14 μg/mL, with a mean half-life of 11.4±6.1 hours. A significant negative correlation existed between postconceptional age and ABK half-life (r=0.64;P<0.05), and there was a positive correlation between postconceptional age and ABK clearance (r=0.83;P<0.05). The NAC index significantly increased after ABK therapy (P<0.05), and a significant positive correlation was found between the though level of ABK and the NAG index after ABK therapy (r=0.84;P<0.05). ABK, similar to other aminoglyoosides, should be used with caution in low-birth-weight infants with careful attention given to their renal function.     

Effect of ciprofloxacin on levels of lipopolysaccharide and cytokines in experimentally induced Gram-negative bacterial pneumonia in mice

This study was performed to examine the ability of ciprofloxacin (CPFX) to suppress the inflammation associated with lipopolysaccharide (LPS) and an inflammatory cytokine in Gram-negative bacterial pneumonia. For this purpose we measured viable cell counts in bronchoalveolar lavage fluid (BALF), LPS concentrations in BALF, and BALF levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in mice exposed to Klebsiella pneumoniae. We used three groups of mice: controls, treated with physiological saline; mice treated with CPFX; and mice treated with ceftadizime (CAZ). The viable cell count in BALF was low in both the CAZ and CPFX groups. LPS values in BALF were significantly lower in the CPFX group than in the CAZ group at 48 and 72 h after K. pneumoniae exposure (48 h, P < 0.001; 72 h, P < 0.05). The BALF TNF-α level was significantly higher in the CAZ group at 24, 48, and 72 h compared to levels in the control and CPFX groups (P < 0.05). In conclusion, these results suggest that CPFX inhibited increases of LPS and TNF-α in Gram-negative bacterial pneumonia, thereby suppressing the lung inflammation that accompanies pneumonia.     

The effect of iNOS deletion on hepatic gluconeogenesis in hyperdynamic murine septic shock

Objective To investigate the role of the inducible nitric oxide synthase activation-induced excess nitric oxide formation on the rate of hepatic glucose production during fully resuscitated murine septic shock. Design Prospective, controlled, randomized animal study. Setting University animal research laboratory. Subjects Male C57Bl/6 and B6.129P2-Nos2^tm1Lau/J (iNOS^−/−) mice. Interventions Fifteen hours after cecal ligation and puncture, anesthetized, mechanically ventilated and instrumented mice (wild-type controls, n = 13; iNOS^−/−, n = 12; wild-type mice receiving 5 mg·kg⁻¹ i.p. of the selective iNOS inhibitor GW274150 immediately after cecal ligation and puncture, n = 8) received continuous i.v. hydroxyethylstarch and norepinephrine to achieve normotensive and hyperdynamic hemodynamics. Measurements and results Measurements were recorded 18, 21 and 24 h after cecal ligation and puncture. Liver microcirculatory perfusion and capillary hemoglobin O₂ saturation (laser Doppler flowmetry and remission spectrophotometry) were well maintained in all groups. Despite significantly lower norepinephrine doses required to achieve the hemodynamic targets, the rate of hepatic glucose production (gas chromatography–mass spectrometry measurements of tissue isotope enrichment during continuous i.v. 1,2,3,4,5,6-¹³C₆-glucose infusion) at 24 h after cecal ligation and puncture was significantly higher in both iNOS^−/− and GW274150-treated mice, which was concomitant with a significantly higher hepatic phosphoenolpyruvate carboxykinase activity (spectrophotometry) in these animals. Conclusions In normotensive, hyperdynamic septic shock, both pharmacologic and genetic deletion of the inducible nitric oxide synthase allowed maintenance of hepatic glucose production, most likely due to maintained activity of the key regulatory enzyme of gluconeogenesis, phosphoenolpyruvate carboxykinase. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. G. Albuszies and J. Vogt contributed equally to this article.     

Nitric oxide synthase inhibition by L-NAME in leukocytopenic patients with severe septic shock

Objectives: To investigate the effects of nitric oxide synthase inhibition by N^G-nitro-l-arginine methyl ester (l-NAME) on hemodynamics and outcome in leukocytopenic ( < 1000/μl) patients with severe septic shock requiring strong vasopressor support. Design: Prospective clinical study. Setting: Medical intensive care unit. Patients: 10 patients with hematologic malignancies in chemotherapy-induced leukocytopenia with severe septic shock and high-dose vasopressor requirement. Intervention: Continuous intravenous infusion of l-NAME (0.3 mg / kg per hour) for a study period of 24 h with prolongation for up to 96 h according to individual requirements. Measurements and results: Compared to baseline values, an increase in mean arterial pressure (p = 0.0021), systemic vascular resistance (p = 0.0001), and left ventricular stroke work index (p = 0.023) with a concomitant decrease in vasopressor requirement (p < 0.05) was observed during the first 24 h of l-NAME treatment. Cardiac output data were unchanged during the study period (p = 0.49). l-NAME was tapered off in five patients who again became responsive to vasopressor medication. Two patients survived the episode of septic shock and vasoactive medication was stopped. Conclusions: The data demonstrate that inhibition of nitric oxide synthase may be beneficial for the treatment of severe septic shock in leukocytopenic patients as indicated by an increase in systemic vascular resistance, mean arterial pressure, and left ventricular stroke work index. Received: 6 June 1996 Accepted: 23 January 1997     

Short-term effects of methylene blue on hemodynamics and gas exchange in humans with septic shock

Objective The aim of this study was to investigate the acute effects of methylene blue (MB), an inhibitor of thel-arginine nitric oxide pathway, in patients with septic shock.Design A prospective, open, single-dose study.Setting The medical ICU of a university hospital.Patients Six patients with severe septic shock.Interventions Complete hemodynamic values were recorded before and 20 min after the infusion of intravenous MB (3 mg kg^–1). Arterial pressure was then monitored during the next 24 h or until death.Measurements and results Methylene blue increased the mean arterial pressure from 69.7±4.5 to 83.7±5.1 mmHg (p=0.028) and the mean pulmonary artery pressure, from 34.3±7.2 to 38.7±8.0 mmHg (p=0.023). Systemic vascular resistance index was increased from 703.1±120.6 to 903.7±152.2 dyne.s.cm^–5.m^–2 (p=0.028) and pulmonary vascular resistance index, from 254.6±96.9 to 342.2±118.9 dyne.s.cm^–5.m^–2 (p=0.027). The PaO₂/FIO₂ decreased from 229.2±54.4 to 162.2±44.1 mmHg (p=0.028), without significant modification of intrapulmonary shunting. Heart rate, cardiac index, right atrial pressure, DO₂, VO₂, oxygen extraction and arterial lactate were essentially unchanged. Sequential measurements of arterial pressure demonstrated a return to baseline level in 2–3 h. All but one patients died, three in shock and two in multiple organ failure.Conclusions MB induces systemic and pulmonary vasoconstriction in patients with septic shock, without significant decrease in cardiac index. The worsening of arterial oxygenation following MB injection may limit its use in patients with the adult respiratory distress syndrome. Larger studies are required to determine whether MB improves the outcome of patients with septic shock.The study was supported by the Délégation à la Recherche Clinique, Assistance Publique-Hôpitaux de Paris