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Stephen R. Marder - One of the best experts on this subject based on the ideXlab platform.
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determination of ziprasidone in human Plasma by liquid chromatography electrospray tandem mass spectrometry and its application to Plasma Level determination in schizophrenia patients
Journal of Chromatography B, 2007Co-Authors: Manickam Aravagiri, Stephen R. Marder, Bruce G PollockAbstract:Abstract An accurate, rapid and simple liquid chromatography–tandem mass spectrometry (LC–MS–MS) assay method was developed for the determination of ziprasidone (ZIP) in the Plasma of schizophrenia patients. A simple one step liquid–liquid extraction with 20% methylene dichloride in pentane was used to isolate ZIP and the internal standard from the Plasma matrix. The compounds were separated on a C-18 column by an isocratic elution and the eluted compounds were analyzed by a triple quadrupole mass spectrometer with a TurboIon spray interface using the positive ion atmospheric pressure electrospray ionization method and detected using multiple reaction monitoring mode. The ZIP standard calibration curve was linear over the range of 0.25–500 ng/ml when 0.5 ml of Plasma was used for the analysis ( r 2 > 0.998). The intra-assay (within-day) and inter-assay (between-day) variations were less than 12% for the spiked standard curve and quality control samples. The absolute extraction efficiency was 82% for ZIP and 68% for INS-RSP. The analysis time for each sample was less than 3 min and useful for high turnaround Plasma Level determinations. This LC–MS–MS assay method for ZIP is highly specific, sensitive, accurate and rapid and is currently being used for the Plasma Level determination of ZIP in schizophrenia patients treated with various daily oral doses of ZIP. The data showed large inter-individual variations.
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fluphenazine Plasma Level monitoring for patients receiving fluphenazine decanoate
Schizophrenia Research, 2002Co-Authors: Stephen R. Marder, Manickam Aravagiri, Donna A Wirshing, Malca B Lebell, William C Wirshing, Jim MintzAbstract:Abstract Background: Finding a dose of an antipsychotic for maintenance therapy that is both safe and effective can be difficult because clinicians are unable to titrate dose against clinical response in patients who are already stable. Therapeutic monitoring of antipsychotic Plasma Levels has the potential for helping clinicians in dosage selection. With this in mind, we evaluated the usefulness of monitoring fluphenazine Plasma Levels for patients with schizophrenia who were receiving maintenance treatment with fluphenazine decanoate. Method: Thirty-one patients with schizophrenia were randomly assigned to low, medium, or high (0.1–0.3, 0.3–0.6, 0.6–1.0 ng/ml) Plasma Levels of fluphenazine. The dose of fluphenazine decanoate was adjusted in order to maintain patients in their assigned range. Side effects, psychopathology, and psychotic exacerbations were measured during the year following randomization. Results: All of the psychotic exacerbations occurred during the first eight weeks following randomization, before patients had adequate time to reach their Plasma Level assignments. We did not find a relationship between Plasma Levels of fluphenazine and clinical outcomes or side effects. Conclusion: Our results do not provide support for the usefulness of monitoring fluphenazine Plasma Levels for patients receiving fluphenazine decanoate.
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simultaneous determination of clozapine and its n desmethyl and n oxide metabolites in Plasma by liquid chromatography electrospray tandem mass spectrometry and its application to Plasma Level monitoring in schizophrenic patients
Journal of Pharmaceutical and Biomedical Analysis, 2001Co-Authors: Manickam Aravagiri, Stephen R. MarderAbstract:A liquid chromatography tandem mass spectrometry (LC-MS-MS) assay method for the simultaneous determination of clozapine and its N-desmethyl (norclozapine) and N-oxide metabolites in human Plasma is described. The compounds were extracted from Plasma by a single step liquid-liquid extraction procedure and analyzed using a high performance liquid chromatography electrospray tandem mass spectrometer system. The compounds were eluted isocratically on a C-18 column, ionized using positive ion atmospheric pressure electrospray ionization method by a TurboIonspray source and analyzed using multiple reaction monitoring mode. The ion transitions monitored were m/z 327 --> m/z 270 for clozapine, m/z 313 --> m/z 192 for norclozapine, m/z 343 --> m/z 256 for clozapine-N-oxide and m/z 421--> m/z 201 for internal standard. The standard curves of clozapine, norclozapine and clozapine-N-oxide were linear over the range of 1 ng/ml to 1000 ng/ml when 0.5 ml of Plasma was used for the analysis (r(2) >0.998). Three pooled Plasma samples collected from patients who were treated with clozapine were used as long-term quality control samples to check the validity of spiked standard curve samples made at various times. The intra- and inter-assay variations for the spiked standard curve and quality control samples were less than 14%. These variations for the long-term patient quality control samples were less than 11%. The LC-MS-MS assay for simultaneous determination of clozapine, norclozapine and clozapine-N-oxide reported here is highly specific, sensitive, accurate and rapid. This method is currently being used for the Plasma Level monitoring of clozapine and its N-desmethyl and N-oxide metabolites in patients treated with clozapine. The Plasma Levels of clozapine, norclozapine and clozapine-N-oxide varied widely within and among patients. The data revealed that the norclozapine and clozapine N-oxide metabolites were present at about 58%+/-14% and 17%+/-6% of clozapine concentrations in Plasma, respectively.
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Plasma Level monitoring of olanzapine in patients with schizophrenia determination by high performance liquid chromatography with electrochemical detection
Therapeutic Drug Monitoring, 1997Co-Authors: Manickam Aravagiri, William C Wirshing, Donna Ames, Stephen R. MarderAbstract:: A sensitive high-performance liquid chromatography method with electrochemical detection for the determination of olanzapine in human Plasma is described. Olanzapine from Plasma samples was isolated by a simple one-step liquid--liquid extraction with 15% methylene chloride in pentane with an extraction recovery of approximately 94% of the total olanzapine in Plasma. The compound was separated on a cyano column. Under the conditions described, commonly coadministered drugs and other common antipsychotic drugs did not interfere with the analysis of olanzapine. The lower limit of determination of the assay was 0.25 ng of olanzapine per ml when 1 ml of Plasma was used for the analysis. The interaassay and intraassay variance was (CV%) less than 10%. The standard curve was linear within the range of 0.25 to 50 ng/ml of olanzapine. This method has been used for the determination of Plasma Levels of olanzapine in patients with schizophrenia who were treated with daily oral doses of 10, 15, and 20 mg of olanzapine. The results indicate that the Plasma Level of olanzapine increases linearly with the administered daily oral dose (r = 0.6889, p = 0.01).
Manickam Aravagiri - One of the best experts on this subject based on the ideXlab platform.
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determination of ziprasidone in human Plasma by liquid chromatography electrospray tandem mass spectrometry and its application to Plasma Level determination in schizophrenia patients
Journal of Chromatography B, 2007Co-Authors: Manickam Aravagiri, Stephen R. Marder, Bruce G PollockAbstract:Abstract An accurate, rapid and simple liquid chromatography–tandem mass spectrometry (LC–MS–MS) assay method was developed for the determination of ziprasidone (ZIP) in the Plasma of schizophrenia patients. A simple one step liquid–liquid extraction with 20% methylene dichloride in pentane was used to isolate ZIP and the internal standard from the Plasma matrix. The compounds were separated on a C-18 column by an isocratic elution and the eluted compounds were analyzed by a triple quadrupole mass spectrometer with a TurboIon spray interface using the positive ion atmospheric pressure electrospray ionization method and detected using multiple reaction monitoring mode. The ZIP standard calibration curve was linear over the range of 0.25–500 ng/ml when 0.5 ml of Plasma was used for the analysis ( r 2 > 0.998). The intra-assay (within-day) and inter-assay (between-day) variations were less than 12% for the spiked standard curve and quality control samples. The absolute extraction efficiency was 82% for ZIP and 68% for INS-RSP. The analysis time for each sample was less than 3 min and useful for high turnaround Plasma Level determinations. This LC–MS–MS assay method for ZIP is highly specific, sensitive, accurate and rapid and is currently being used for the Plasma Level determination of ZIP in schizophrenia patients treated with various daily oral doses of ZIP. The data showed large inter-individual variations.
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fluphenazine Plasma Level monitoring for patients receiving fluphenazine decanoate
Schizophrenia Research, 2002Co-Authors: Stephen R. Marder, Manickam Aravagiri, Donna A Wirshing, Malca B Lebell, William C Wirshing, Jim MintzAbstract:Abstract Background: Finding a dose of an antipsychotic for maintenance therapy that is both safe and effective can be difficult because clinicians are unable to titrate dose against clinical response in patients who are already stable. Therapeutic monitoring of antipsychotic Plasma Levels has the potential for helping clinicians in dosage selection. With this in mind, we evaluated the usefulness of monitoring fluphenazine Plasma Levels for patients with schizophrenia who were receiving maintenance treatment with fluphenazine decanoate. Method: Thirty-one patients with schizophrenia were randomly assigned to low, medium, or high (0.1–0.3, 0.3–0.6, 0.6–1.0 ng/ml) Plasma Levels of fluphenazine. The dose of fluphenazine decanoate was adjusted in order to maintain patients in their assigned range. Side effects, psychopathology, and psychotic exacerbations were measured during the year following randomization. Results: All of the psychotic exacerbations occurred during the first eight weeks following randomization, before patients had adequate time to reach their Plasma Level assignments. We did not find a relationship between Plasma Levels of fluphenazine and clinical outcomes or side effects. Conclusion: Our results do not provide support for the usefulness of monitoring fluphenazine Plasma Levels for patients receiving fluphenazine decanoate.
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simultaneous determination of clozapine and its n desmethyl and n oxide metabolites in Plasma by liquid chromatography electrospray tandem mass spectrometry and its application to Plasma Level monitoring in schizophrenic patients
Journal of Pharmaceutical and Biomedical Analysis, 2001Co-Authors: Manickam Aravagiri, Stephen R. MarderAbstract:A liquid chromatography tandem mass spectrometry (LC-MS-MS) assay method for the simultaneous determination of clozapine and its N-desmethyl (norclozapine) and N-oxide metabolites in human Plasma is described. The compounds were extracted from Plasma by a single step liquid-liquid extraction procedure and analyzed using a high performance liquid chromatography electrospray tandem mass spectrometer system. The compounds were eluted isocratically on a C-18 column, ionized using positive ion atmospheric pressure electrospray ionization method by a TurboIonspray source and analyzed using multiple reaction monitoring mode. The ion transitions monitored were m/z 327 --> m/z 270 for clozapine, m/z 313 --> m/z 192 for norclozapine, m/z 343 --> m/z 256 for clozapine-N-oxide and m/z 421--> m/z 201 for internal standard. The standard curves of clozapine, norclozapine and clozapine-N-oxide were linear over the range of 1 ng/ml to 1000 ng/ml when 0.5 ml of Plasma was used for the analysis (r(2) >0.998). Three pooled Plasma samples collected from patients who were treated with clozapine were used as long-term quality control samples to check the validity of spiked standard curve samples made at various times. The intra- and inter-assay variations for the spiked standard curve and quality control samples were less than 14%. These variations for the long-term patient quality control samples were less than 11%. The LC-MS-MS assay for simultaneous determination of clozapine, norclozapine and clozapine-N-oxide reported here is highly specific, sensitive, accurate and rapid. This method is currently being used for the Plasma Level monitoring of clozapine and its N-desmethyl and N-oxide metabolites in patients treated with clozapine. The Plasma Levels of clozapine, norclozapine and clozapine-N-oxide varied widely within and among patients. The data revealed that the norclozapine and clozapine N-oxide metabolites were present at about 58%+/-14% and 17%+/-6% of clozapine concentrations in Plasma, respectively.
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Plasma Level monitoring of olanzapine in patients with schizophrenia determination by high performance liquid chromatography with electrochemical detection
Therapeutic Drug Monitoring, 1997Co-Authors: Manickam Aravagiri, William C Wirshing, Donna Ames, Stephen R. MarderAbstract:: A sensitive high-performance liquid chromatography method with electrochemical detection for the determination of olanzapine in human Plasma is described. Olanzapine from Plasma samples was isolated by a simple one-step liquid--liquid extraction with 15% methylene chloride in pentane with an extraction recovery of approximately 94% of the total olanzapine in Plasma. The compound was separated on a cyano column. Under the conditions described, commonly coadministered drugs and other common antipsychotic drugs did not interfere with the analysis of olanzapine. The lower limit of determination of the assay was 0.25 ng of olanzapine per ml when 1 ml of Plasma was used for the analysis. The interaassay and intraassay variance was (CV%) less than 10%. The standard curve was linear within the range of 0.25 to 50 ng/ml of olanzapine. This method has been used for the determination of Plasma Levels of olanzapine in patients with schizophrenia who were treated with daily oral doses of 10, 15, and 20 mg of olanzapine. The results indicate that the Plasma Level of olanzapine increases linearly with the administered daily oral dose (r = 0.6889, p = 0.01).
Janet M Wells - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetically designed double blind placebo controlled study of nortriptyline in 6 to 12 year olds with major depressive disorder
Journal of the American Academy of Child and Adolescent Psychiatry, 1992Co-Authors: B Geller, T B Cooper, D L Graham, F A Marsteller, Harriet H Fetner, Janet M WellsAbstract:Abstract A random assignment, double-blind, placebo-controlled study of nortriptyline in 50 prepubertal 6− to 12-year-olds with Research Diagnostic Criteria and DSM-III major depressive disorder was performed. The protocol included a 2-week placebo wash-out phase and an 8-week double-blind, placebo-controlled phase with weekly Plasma Level monitoring. Active subjects had their Plasma Level pharmacokinetically placed at 80 ± 20 ng/ ml by using previously developed tables to determine the starting dose from a Plasma Level 24 hours after a single dose administered at baseline. The mean Plasma Level was 89.9 ng/ml. The study population was severely depressed, had a chronic, unremitting course of long duration before the study, had a high percentage of family histories with affective disorder, alcoholism and suicidality, and had a high rate of comorbidity. None of the subjects had ever received tricyclic antidepressants before this study. There was a poor rate of response in both treatment groups (30.8% active, 16.7% placebo). Active subjects did not evidence the anticholinergic side effects reported in adult samples. The implications of these findings for future pharmacotherapy studies of depressed children are discussed. J. Am. Acad. Child Adolesc. Psychiatry , 1992, 31, 1:34–44.
Masahiko Kinoshita - One of the best experts on this subject based on the ideXlab platform.
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interleukin 6 spillover in the peripheral circulation increases with the severity of heart failure and the high Plasma Level of interleukin 6 is an important prognostic predictor in patients with congestive heart failure
Journal of the American College of Cardiology, 1998Co-Authors: Takayoshi Tsutamoto, Tomoko Hisanaga, Atsuyuki Wada, Keiko Maeda, Masato Ohnishi, Daisuke Fukai, Naoko Mabuchi, Masahide Sawaki, Masahiko KinoshitaAbstract:Abstract Objectives. We 1) evaluated whether interleukin-6 (IL-6) is produced in the peripheral circulation in patients with congestive heart failure (CHF), 2) estimated the factors for increased IL-6, and 3) clarified the prognostic role of high Plasma Levels of IL-6 in patients with CHF. Background. Although Plasma Levels of IL-6 have been reported to increase in patients with CHF, and production of IL-6 in endothelial cells and vascular smooth muscle cells has been postulated from in vitro studies, the origin of the increase of IL-6 in CHF remains unknown. Moreover, the prognostic value of a high Plasma Level of IL-6, independent of classic neurohumoral factors, remains to be elucidated. Methods. A comparison was made of the Plasma Levels of IL-6 between the femoral artery and the femoral vein in 13 normal subjects and in 80 patients with CHF. In another study, we measured Plasma IL-6 in 100 patients with CHF and follow-up data. Results. Plasma IL-6 Levels increased significantly from the femoral artery to the femoral vein in normal subjects and in patients with CHF. Arteriovenous IL-6 spillover in the leg increased with the severity of CHF. Among the hemodynamic variables and the various neurohumoral factors, the Plasma norepinephrine (NE) Level showed an independent and significant positive relation with the Plasma IL-6 Level in patients with CHF. Moreover, treatment with beta-adrenergic blocking agents showed an independent and significant negative relation with Plasma IL-6 Levels. In 100 patients, Plasma IL-6 (p Conclusions. Our findings indicate that the IL-6 spillover in the peripheral circulation increases with the severity of CHF and that the increase in Plasma IL-6 is mainly associated with the activation of the sympathetic nervous system. High Plasma Levels of IL-6 can provide prognostic information in patients with CHF, independent of left ventricular ejection fraction and Plasma NE, suggesting an important role for IL-6 in the pathophysiology of CHF.
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prognostic value of Plasma soluble intercellular adhesion molecule 1 and endothelin 1 concentration in patients with chronic congestive heart failure
American Journal of Cardiology, 1995Co-Authors: Takayoshi Tsutamoto, Tomoko Hisanaga, Atsuyuki Wada, Keiko Maeda, Daisuke Fukai, Yukiharu Maeda, Masahiko KinoshitaAbstract:Abstract We tested the hypothesis that Plasma endothelin-1 (ET-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with congestive heart failure (CHF) are related to subsequent survival, and assessed whether the measurements of these substances provide additional prognostic information to that obtained from clinical and biochemical variables previously known to be associated with high mortality. Plasma Levels of sICAM-1 and ET-1 were measured in 102 patients with CHF (left ventricular ejection fraction [LVEF] 18 months. The Plasma Level of sICAM-1 increased with the severity of CHF (normal, 149 ± 10 ng/ml, mild CHF [New York Heart Association functional class II], 207 ± 9.4 ng/ml, severe CHF [functional class III or IV], 293 ± 18 ng/ml). The Plasma Level of ET-1 also increased with the severity of CHF (normal, 1.5 ± 0.2 pg/ml, mild CHF, 2.1 ± 0.1 pg/ml, severe CHF, 4.0 ± 0.4 pg/ml). Plasma Levels of both sICAM-1 and ET-1 decreased after treatment in 14 patients, with improvements in symptoms (from functional class IV to II) during the follow-up period. There was a significant positive correlation between the Plasma Level of ET-1 and Plasma sICAM-1 (r = 0.44, p
Takayoshi Tsutamoto - One of the best experts on this subject based on the ideXlab platform.
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Plasma Level of cardiotrophin 1 as a prognostic predictor in patients with chronic heart failure
European Journal of Heart Failure, 2007Co-Authors: Takayoshi Tsutamoto, Atsuyuki Wada, Masato Ohnishi, Shigeru Asai, Toshinari Tanaka, Hiroshi Sakai, Keizo Nishiyama, Masanori Fujii, Takashi Yamamoto, Yoshihiko SaitoAbstract:Background: Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines and is increased in patients with chronic heart failure (CHF). Aims: To evaluate the prognostic role of CT-1 in patients with CHF. Methods and results: We measured the Plasma Levels of CT-1, brain natriuretic peptide (BNP), and IL-6 in 125 patients with CHF. Patients were monitored for a mean follow-up period of 2.9years. Plasma Levels of CT-1 increased with severity of CHF. There was a significant negative correlation between Plasma CT-1 and left ventricular ejection fraction. There was a significant correlation between Plasma CT-1 and log IL-6. During the follow-up period, 37 patients died. High Plasma Levels of CT-1, BNP, and IL-6 were independent predictors of mortality on stepwise multivariate analysis. The hazard ratio for mortality in patients with Plasma BNP>170pg/mL and CT-1>658fmol/mL was 2.48 (95% confidence interval, 1.217–5.060) compared to those with Plasma BNP>170pg/mL and CT-1<658fmol/mL (p=0.0124). Conclusion: These findings indicate that Plasma CT-1 measurement provides additional prognostic information and that combined Levels of CT-1 and BNP are more accurate at predicting mortality in patients with CHF than either marker alone.
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interleukin 6 spillover in the peripheral circulation increases with the severity of heart failure and the high Plasma Level of interleukin 6 is an important prognostic predictor in patients with congestive heart failure
Journal of the American College of Cardiology, 1998Co-Authors: Takayoshi Tsutamoto, Tomoko Hisanaga, Atsuyuki Wada, Keiko Maeda, Masato Ohnishi, Daisuke Fukai, Naoko Mabuchi, Masahide Sawaki, Masahiko KinoshitaAbstract:Abstract Objectives. We 1) evaluated whether interleukin-6 (IL-6) is produced in the peripheral circulation in patients with congestive heart failure (CHF), 2) estimated the factors for increased IL-6, and 3) clarified the prognostic role of high Plasma Levels of IL-6 in patients with CHF. Background. Although Plasma Levels of IL-6 have been reported to increase in patients with CHF, and production of IL-6 in endothelial cells and vascular smooth muscle cells has been postulated from in vitro studies, the origin of the increase of IL-6 in CHF remains unknown. Moreover, the prognostic value of a high Plasma Level of IL-6, independent of classic neurohumoral factors, remains to be elucidated. Methods. A comparison was made of the Plasma Levels of IL-6 between the femoral artery and the femoral vein in 13 normal subjects and in 80 patients with CHF. In another study, we measured Plasma IL-6 in 100 patients with CHF and follow-up data. Results. Plasma IL-6 Levels increased significantly from the femoral artery to the femoral vein in normal subjects and in patients with CHF. Arteriovenous IL-6 spillover in the leg increased with the severity of CHF. Among the hemodynamic variables and the various neurohumoral factors, the Plasma norepinephrine (NE) Level showed an independent and significant positive relation with the Plasma IL-6 Level in patients with CHF. Moreover, treatment with beta-adrenergic blocking agents showed an independent and significant negative relation with Plasma IL-6 Levels. In 100 patients, Plasma IL-6 (p Conclusions. Our findings indicate that the IL-6 spillover in the peripheral circulation increases with the severity of CHF and that the increase in Plasma IL-6 is mainly associated with the activation of the sympathetic nervous system. High Plasma Levels of IL-6 can provide prognostic information in patients with CHF, independent of left ventricular ejection fraction and Plasma NE, suggesting an important role for IL-6 in the pathophysiology of CHF.
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prognostic value of Plasma soluble intercellular adhesion molecule 1 and endothelin 1 concentration in patients with chronic congestive heart failure
American Journal of Cardiology, 1995Co-Authors: Takayoshi Tsutamoto, Tomoko Hisanaga, Atsuyuki Wada, Keiko Maeda, Daisuke Fukai, Yukiharu Maeda, Masahiko KinoshitaAbstract:Abstract We tested the hypothesis that Plasma endothelin-1 (ET-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with congestive heart failure (CHF) are related to subsequent survival, and assessed whether the measurements of these substances provide additional prognostic information to that obtained from clinical and biochemical variables previously known to be associated with high mortality. Plasma Levels of sICAM-1 and ET-1 were measured in 102 patients with CHF (left ventricular ejection fraction [LVEF] 18 months. The Plasma Level of sICAM-1 increased with the severity of CHF (normal, 149 ± 10 ng/ml, mild CHF [New York Heart Association functional class II], 207 ± 9.4 ng/ml, severe CHF [functional class III or IV], 293 ± 18 ng/ml). The Plasma Level of ET-1 also increased with the severity of CHF (normal, 1.5 ± 0.2 pg/ml, mild CHF, 2.1 ± 0.1 pg/ml, severe CHF, 4.0 ± 0.4 pg/ml). Plasma Levels of both sICAM-1 and ET-1 decreased after treatment in 14 patients, with improvements in symptoms (from functional class IV to II) during the follow-up period. There was a significant positive correlation between the Plasma Level of ET-1 and Plasma sICAM-1 (r = 0.44, p