Influence of Midazolam on the Plasma Concentrations of Mepivacaine Afte Lumbar Epidural Injection in Children

Background Epidural administration of morphine is a common analgesic technique to manage pain. Morphine spreads from the epidural space to the cerebrospinal fluid and then rostrally, causing side effects mediated by the brain stem. However, data on the rostral spread of morphine-mediated analgesia are sparse. This study examined the rostral spread of analgesic effects on heat and electrical pain after epidural administration of morphine. Methods In a randomized, double-blinded, placebo-controlled, crossover study, 5 mg morphine or saline placebo were injected into the lumbar epidural space in nine healthy volunteers. Correct needle placement was confirmed with fluoroscopy. Analgesia to experimental nociceptive heat and electrical stimuli was measured at lumbar (L4), thoracic (T10), cervical (C2), and trigeminal (V2) levels before and 2, 5, 10, and 24 h after epidural injection. Plasma samples for assaying morphine concentrations were drawn before and after each analgesic evaluation. Results Epidural morphine significantly attenuated experimental heat pain at all dermatomes tested compared with saline placebo. Analgesic effects were significant at L4 after 2, 5, and 10 h, at T10 after 5, 10, and 24 h, and at V2 after 10 h. Electrical pain was attenuated at the lumbar and thoracic but not at the cervical dermatome. Analgesic effects were significant at L4 after 2, 5, and 10 h and at T10 after 5 and 10 h. Morphine plasma concentrations were below the detection limit (1 ng/ml) in eight of the nine subjects 10 h after epidural injection. Conclusions Lumbar epidural injection of morphine attenuated cutaneous heat pain up to the trigeminal dermatome during a 24-h observation period. In a clinical context, this implies that some types of pain may be attenuated up to the supraspinal level after lumbar epidural administration of morphine.

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Variations Across the Menstrual Cycle in EEG Activity During Thinking and Mental Relaxation

Journal of Psychophysiology ◽

10.1027//0269-8803.13.3.163 ◽

1999 ◽

Vol 13 (3) ◽

pp. 163-172 ◽

Cited By ~ 7

Author(s):

R. Krug ◽

M. Mölle ◽

H.L. Fehm ◽

J. Born

Keyword(s):

Menstrual Cycle ◽

Divergent Thinking ◽

Spectral Power ◽

Plasma Concentrations ◽

Task Demands ◽

Menstrual Phase ◽

Convergent Thinking ◽

Eeg Activity ◽

Dimensional Complexity ◽

Mental Relaxation

Abstract Previous studies have indicated: (1) peak performance on tests of divergent creative thinking during the ovulatory phase of the menstrual cycle; (2) compared to convergent analytical thinking, divergent thinking was found to be associated with a distinctly increased dimensional complexity of ongoing EEG activity. Based on these findings, we hypothesized that cortical information processing during the ovulatory phase is characterized by an increased EEG dimensionality. Each of 16 women was tested on 3 occasions: during the ovulatory phase, the luteal phase, and menses. Presence of the phases was confirmed by determination of plasma concentrations of estradiol, progesterone, and luteinizing hormone. The EEG was recorded while the women performed: (1) tasks of divergent thinking; (2) tasks of convergent thinking; and (3) during mental relaxation. In addition to EEG dimensional complexity, conventional spectral power analysis was performed. Behavioral data confirmed enhanced creative performance during the ovulatory phase while convergent thinking did not vary across cycle phases. EEG complexity was higher during divergent than convergent thought, but this difference remained unaffected by the menstrual phase. Influences of the menstrual phase on EEG activity were most obvious during mental relaxation. In this condition, women during the ovulatory phase displayed highest EEG dimensionality as compared with the other cycle phases, with this effect being most prominent over the central and parietal cortex. Concurrently, power within the alpha frequency band as well as theta power at frontal and parietal leads were lower during the luteal than ovulatory phase. EEG results indicate that task demands of thinking overrode effects of menstrual cycle. However, with a less demanding situation, an ovulatory increase in EEG dimensionality became prominent suggesting a loosening of associative habits during this phase.

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P2353 Supplementary treatment with abacorS, a soy protein based dietary supplement, reduces plasma concentrations of total and LDL cholesterols in statin-treated hypercholesterolemic patients

European Heart Journal ◽

10.1016/s0195-668x(03)95347-4 ◽

2003 ◽

Vol 24 (5) ◽

pp. 458 ◽

Cited By ~ 1

Author(s):

P CLAUSEN

Keyword(s):

Dietary Supplement ◽

Soy Protein ◽

Plasma Concentrations ◽

Supplementary Treatment

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Very Low Activated Factor VII and Reduced Factor VII Antigen in Familial Abetalipoproteinaemia

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615179 ◽

1998 ◽

Vol 80 (08) ◽

pp. 233-238 ◽

Cited By ~ 8

Author(s):

K. A. Mitropoulos ◽

M. N. Nanjee ◽

D. J. Howarth ◽

J. C. Martin ◽

M. P. Esnouf ◽

...

Keyword(s):

Plasma Concentrations ◽

Positive Association ◽

Factor Ix ◽

Factor Vii ◽

Unesterified Fatty Acid ◽

Factor Xii ◽

Factor X ◽

Factor Xi ◽

Activated Factor Vii ◽

Normal Mean

SummaryAbetalipoproteinaemia is a rare disorder of apolipoprotein B metabolism associated with extremely low plasma concentrations of triglyce-ride. To discover whether the general positive association between factor VII and triglyceride levels extends to this condition, 5 patients were compared with 18 controls. All patients had a triglyceride below 100 μmol/l. Plasma unesterified fatty acid concentration was normal. Although factor IX activity was only slightly reduced (mean 88% standard) and factor IX antigen was normal, mean activated factor VII in patients was strikingly reduced to 34% of that in controls, a level similar to that found in haemophilia B. The patients’ mean factor VII activity and factor VII antigen were also significantly reduced to 54% and 63% of those in controls, respectively. Mean factor XI activity and tissue factor pathway inhibitor activity were reduced in patients to 70% and 75% of control values respectively, while factor XII, factor XI antigen, factor X, prothrombin and protein C were normal.

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Parallel Reduction of Plasma Levels of High and Low Molecular Weight Kininogen in Patients with Cirrhosis

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614849 ◽

1999 ◽

Vol 82 (11) ◽

pp. 1428-1432 ◽

Cited By ~ 9

Author(s):

Cheryl Scott ◽

Francesco Salerno ◽

Elettra Lorenzano ◽

Werner Müller-Esterl ◽

Angelo Agostoni ◽

...

Keyword(s):

Molecular Weight ◽

Liver Disease ◽

Liver Function ◽

Plasma Levels ◽

Plasma Concentrations ◽

Normal Subjects ◽

Low Molecular Weight ◽

Major Band ◽

Sds Page ◽

Normal Controls

SummaryLittle is known about the regulation of high-molecular-weight-kininogen (HK) and low-molecular-weight-kininogen (LK) or the relationship of each to the degree of liver function impairment in patients with cirrhosis. In this study, we evaluated HK and LK quantitatively by a recently described particle concentration fluorescence immunoassay (PCFIA) and qualitatively by SDS PAGE and immunoblotting analyses in plasma from 33 patients with cirrhosis presenting various degrees of impairment of liver function. Thirty-three healthy subjects served as normal controls. Patients with cirrhosis had significantly lower plasma levels of HK (median 49 μg/ml [range 22-99 μg/ml]) and LK (58 μg/ml [15-100 μg/ml]) than normal subjects (HK 83 μg/ml [65-115 μg/ml]; LK 80 μg/ml [45-120 μg/ml]) (p < 0.0001). The plasma concentrations of HK and LK were directly related to plasma levels of cholinesterase (P < 0.0001) and albumin (P < 0.0001 and P < 0.001) and inversely to the Child-Pugh score (P < 0.0001) and to prothrombin time ratio (P < 0.0001) (reflecting the clinical and laboratory abnormalities in liver disease). Similar to normal individuals, in patients with cirrhosis, plasma HK and LK levels paralleled one another, suggesting that a coordinate regulation of those proteins persists in liver disease. SDS PAGE and immunoblotting analyses of kininogens in cirrhotic plasma showed a pattern similar to that observed in normal controls for LK (a single band at 66 kDa) with some lower molecular weight forms noted in cirrhotic plasma. A slight increase of cleavage of HK (a major band at 130 kDa and a faint but increased band at 107 kDa) was evident. The increased cleavage of HK was confirmed by the lower cleaved kininogen index (CKI), as compared to normal controls. These data suggest a defect in hepatic synthesis as well as increased destructive cleavage of both kininogens in plasma from patients with cirrhosis. The decrease of important regulatory proteins like kininogens may contribute to the imbalance in coagulation and fibrinolytic systems, which frequently occurs in cirrhotic patients.

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Plasma Thrombospondin as an Indicator of Intravascular Platelet Activation in Patients with Vasculitis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646003 ◽

1987 ◽

Vol 58 (03) ◽

pp. 850-852 ◽

Cited By ~ 15

Author(s):

M B McCrohan ◽

S W Huang ◽

J W Sleasman ◽

P A Klein ◽

K J Kao

Keyword(s):

Platelet Activation ◽

Plasma Levels ◽

Half Life ◽

Degradation Products ◽

Plasma Concentrations ◽

Primary Source ◽

Positive Correlation ◽

Activation Marker ◽

Fibrin Degradation Products ◽

The Mean

SummaryThe use of plasma thrombospondin (TSP) concentration was investigated as an indicator of intravascular platelet activation. Patients (n = 20) with diseases that have known vasculitis were included in the study. The range and the mean of plasma TSP concentrations of patients with vasculitis were 117 ng/ml to 6500 ng/ml and 791±1412 ng/ml (mean ± SD); the range and the mean of plasma TSP concentrations of control individuals (n = 33) were 13 ng/ml to 137 ng/ml and 59±29 ng/ml. When plasma TSP concentrations were correlated with plasma concentrations of another platelet activation marker, β-thromboglobulin (P-TG), it was found that the TSP concentration inei eased exponentially as the plasma β-TG level rose. A positive correlation between plasma levels of plasma TSP and serum fibrin degradation products was also observed. The results suggest that platelets are the primary source of plasma TSP in patients with various vasculitis and that plasma TSP can be a better indicator than β-TG to assess intravascular platelet activation due to its longer circulation half life.

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Plasma D Dimer: A Useful Marker of Fibrin Breakdown in Renal Failure

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646627 ◽

1989 ◽

Vol 61 (03) ◽

pp. 522-525 ◽

Cited By ~ 32

Author(s):

M P Gordge ◽

R W Faint ◽

P B Rylance ◽

H Ireland ◽

D A Lane ◽

...

Keyword(s):

Renal Failure ◽

Renal Function ◽

Acute Renal Failure ◽

Monoclonal Antibodies ◽

Diabetic Nephropathy ◽

Renal Disease ◽

Plasma Concentrations ◽

Significant Negative Correlation ◽

Healthy Controls ◽

D Dimer

SummaryD dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 ± 3l ng/ml) (mean ± SEM) and diabetic nephropathy (308 ± 74 ng/ml), when compared with healthy controls (96 ± 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 ± 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure.

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Comparison of Specific Antibody, D-Phe-Pro-Arg-CH2Cl and Aprotinin for Prevention of In Vitro Effects of Recombinant Tissue-Type Plasminogen Activator on Haemostasis Parameters

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646016 ◽

1987 ◽

Vol 58 (03) ◽

pp. 921-926 ◽

Cited By ~ 21

Author(s):

E Seifried ◽

P Tanswell

Keyword(s):

Specific Antibody ◽

Plasma Concentrations ◽

Fibrinolytic Therapy ◽

Tissue Type ◽

Control Value ◽

Type Plasminogen Activator ◽

In Vitro Effects ◽

Fibrinolytic Parameters

SummaryIn vitro, concentration-dependent effects of rt-PA on a range of coagulation and fibrinolytic assays in thawed plasma samples were investigated. In absence of a fibrinolytic inhibitor, 2 μg rt-PA/ml blood (3.4 μg/ml plasma) caused prolongation of clotting time assays and decreases of plasminogen (to 44% of the control value), fibrinogen (to 27%), α2-antiplasmin (to 5%), FV (to 67%), FVIII (to 41%) and FXIII (to 16%).Of three inhibitors tested, a specific polyclonal anti-rt-PA antibody prevented interferences in all fibrinolytic and most clotting assays. D-Phe-Pro-Arg-CH2Cl (PPACK) enabled correct assays of fibrinogen and fibrinolytic parameters but interfered with coagulometric assays dependent on endogenous thrombin generation. Aprotinin was suitable only for a restricted range of both assay types.Most in vitro effects were observed only with rt-PA plasma concentrations in excess of therapeutic values. Nevertheless it is concluded that for clinical application, collection of blood samples on either specific antibody or PPACK is essential for a correct assessment of in vivo effects of rt-PA on the haemostatic system in patients undergoing fibrinolytic therapy.

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Species Specific Immunoassays to Measure Blood Platelet and Coagulation Activation in the Rat

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650711 ◽

1996 ◽

Vol 76 (06) ◽

pp. 1090-1095 ◽

Cited By ~ 9

Author(s):

C Ravanat ◽

M Freund ◽

S Schuhler ◽

P Grunert ◽

L Meyer ◽

...

Keyword(s):

Antithrombin Iii ◽

Plasma Concentrations ◽

Simultaneous Detection ◽

Blood Platelet ◽

Coagulation Activation ◽

Platelet Factor ◽

Prethrombotic State ◽

Low Levels ◽

Species Specific ◽

Higher Sensitivity

SummaryThe purpose of this study was to develop specific and sensitive immunoassays to detect early indices of hypercoagulability in the rat. Rat platelet factor 4 (rPF4) and rat fibrinopeptide A (rFPA) assays, tools for the detection of activation of platelets and coagulation respectively, were designed using antibodies raised against purified rPF4 and against synthetic rFPA. The relevance of these new assays and of the commercially available ELISA kit for thrombin-antithrombin III (TAT) complexes was demonstrated in a rat model of a prethrombotic state induced by intravenous infusion of varying doses of thromboplastin (90 to 2400 μl/kg/h). In this model, the immunoassays allowed simultaneous detection of low levels of rFPA and rPF4 which were correlated with fibrinogen and platelet consumption and TAT generation and further proved to be of higher sensitivity than the classical methods of platelet count or measurement of fibrinogen levels. Plasma concentrations of rFPA, rPF4 and TAT were dependent on infusion time and thromboplastin dose, while hirudin (1 mg/kg) prevented their appearance. Thus the new specific immunoassays for rPF4 and rFPA and the commercial human TAT assay represent useful tools for pathophysiological studies or the screening of antithrombotic drugs in rats.

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