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PubMed1985

Long-term control of plasma calcitriol concentration in dogs and humans. Dominant role of plasma calcium concentration in experimental hyperparathyroidism.

Despite great interest in the elevated circulating levels of calcitriol (1,25-[OH]2D) associated with the clinical syndrome of human primary hyperparathyroidism, the relative potencies of known and potential stimuli/suppressors of long-term calcitriol levels have not been evaluated in either clinical or experimentally induced hyperparathyroid states. Based on reports that aparathyroid animals exhibit suppressed plasma calcitriol concentration and that acute administration of parathyroid hormone (PTH) to both humans and experimental animals or to renal slices in vitro results in increased plasma calcitriol concentration/production rate, it might be predicted that a chronic experimental model of either hypercalcemic primary hyperparathyroidism or hypocalcemic secondary hyperparathyroidism would show increased plasma calcitriol concentration. Chronic alterations in plasma calcium concentration have not been implicated as modulating calcitriol levels in any species. Accordingly, we investigated the long-term response of plasma calcitriol concentration in states of sustained experimental primary and secondary hyperparathyroidism. Intact dogs (group I) undergoing continuous intravenous PTH infusion for 12 d developed sustained hypercalcemia and hypophosphatemia, and plasma calcitriol concentration decreased from 23 +/- 3 to 14 +/- 3 pg/ml (P less than 0.01). Subsequent chelator (EGTA)-induced chronic normalization of hypercalcemia during ongoing PTH infusion resulted in a large and sustained increase in plasma calcitriol concentration to supernormal levels, reversible during subsequent cessation of chelator infusion. In additional intact dogs (group II), chronic chelator-induced hypocalcemic secondary hyperparathyroidism resulted in a sustained increase in plasma calcitriol concentration despite hyperphosphatemia. In normal human subjects undergoing a 12-13-d continuous intravenous PTH infusion to result in sustained moderate hypercalcemia (12.0 +/- 0.2 mg/100 ml) and hypophosphatemia, plasma calcitriol concentration decreased significantly (P less than 0.01) as in group I dogs and was followed by reversal to normal levels in a recovery period. The present results provide strong evidence in both humans and dogs that during experimentally induced chronic PTH excess, alterations in plasma calcium concentration dictate the directional response of circulating calcitriol concentrations. The long-term potency of plasma calcium concentration as a modulator of calcitriol metabolism is sufficient to override opposing modulation by plasma phosphorus concentration and PTH.

25-Hydroxyvitamin D 2↗

PubMed2005

[Total and ionized magnesium concentration in the blood plasma and erythrocytic magnesium concentration of women in the third trimester of pregnancy with imminent preterm labor].

OBJECTIVES: There are some data concerning magnesium concentration influence on the risk of preterm labor. The estimation of magnesium concentration changes may be useful in prevention of preterm labor. DESIGN: Therefore the aim of our study was to find out the correlation between magnesium concentration and the risk of preterm labor. MATERIALS AND METHODS: Total magnesium concentration and ionized magnesium concentration in blood plasma and erythrocytic magnesium concentration ware examined in the three groups of: 23 women in the third trimester of pregnancy with imminent preterm labor under tocolytic therapy; 20 women in the third trimester of physiologic pregnancy and 19 non-pregnant healthy women in the reproductive age. RESULTS: We discovered statistically confirmed differences (p < 0,05 ) in ionized magnesium concentration as well between the group of women in physiologic pregnancy and non-pregnant women and between the group of pregnant women with imminent preterm labor and non-pregnant women. CONCLUSIONS: Although there were no statistically confirmed differences in total magnesium concentration and erythrocytic magnesium concentration between the three groups of examined women, there were statistically confirmed differences in ionized magnesium concentration between the pregnant and non-pregnant women. Our results suggest that ionized magnesium concentration is better indicator of magnesium balance in human's body than total magnesium concentration.

Adolescent↗

PubMed2005

[Serum leptin concentration and sympathetic activation estimated on the adrenaline and noradrenaline serum concentration in patients with obstructive sleep apnea].

UNLABELLED: Hypertension, coronary heart diseases, obesity, diabetes mellitus are often present in patients with obstructive sleep apnea (OSA). The aim of the study was to estimate the serum leptin concentration and sympathetic activity in patients with obstructive sleep apnea and in control group. INVESTIGATED GROUP: 51 persons (F6, M45) were included into the study. The control group (GK) consisted of 15 snoring person (15 M) in the age x = 44.19 +/- 14.60, study group (GB) consisted of 36 patients with OSA (6F, 30M) in the age 5 1.47 +/- 8.95 years. METHODS: Leptin was measured by RIA methods using the HUMAN LEPTIN RIA KIT (LINCO Research, Inc).: adrenaline and noradrenaline were measured in the serum by HPLC methods (BIO-RAD). RESULTS: The serum concentrations of leptin (ng/mL), adrenaline and noradrenaline (pg/mL) in patients with OSA compared with control group were respectively 15.55 +/- 11.26 : 61.2 +/- 27.4: 523.2 +/- 165.1 vs 10.34+/- 6.86 : 47.7 +/- 27.3: 447.9 +/- 102.6. There was positive significant correlation between leptin concentration and BMI (r = 0,34) and serum leptin and adrenalin concentration (r = 0,34). The serum leptin concentration was significantly higher in the female group. In the male group there was tendency to increase leptin concentration together with degree of OSA grade estimated by AHI and AHI <50 leptin concentration 12.23+/- 6.96 ng/mL vs AHI>50 and leptin concentration 13.35 +/- 3.54ng/ml. CONCLUSIONS: 1. In the group of patients with OSA the serum concentrations of leptin, adrenaline and noradrenaline were higher then in control group. 2. There are positive statistical significant correlation between serum leptin levels and BMI and serum adrenaline concentration in the study group. 3. The serum leptin concentration was higher in the female group. 4. There was tendency to increased leptin concentration in the study group together with degree of OSA grade estimated by AHI. 5. Our results confirm correlation between leptin and sympathetic activity and their influences on obesity and degree of OSA grade in studied group.

Adult↗

PubMed1991

The Los Angeles TEAM Study: personal exposures, indoor-outdoor air concentrations, and breath concentrations of 25 volatile organic compounds.

The U.S. Environmental Protection Agency and the California Air Resources Board studied the exposures of 51 residents of Los Angeles, California, to 25 volatile organic chemicals (VOCs) in air and drinking water in 1987. A major goal of the study was to measure personal, indoor, and outdoor air concentrations, and breath concentrations of VOCs in persons living in households that had previously been measured in 1984. Other goals were to confirm the marked day-night and seasonal differences observed in 1984; to determine room-to-room variability within homes; to determine source emission rates by measuring air exchange rates in each home; and to extend the coverage of chemicals by employing additional sampling and analysis methods. A total of 51 homes were visited in February of 1987, and 43 of these were revisited in July of 1987. The results confirmed previous TEAM Study findings of higher personal and indoor air concentrations than outdoor concentrations of all prevalent chemicals (except carbon tetrachloride); higher personal, indoor, and outdoor air concentrations in winter than in summer; and (in winter only) higher outdoor concentrations at night than in the daytime. New findings included the following: (1) room-to-room variability of 12-hour average concentrations was very small, indicating that a single monitor may be adequate for estimating indoor concentrations over this time span; (2) "whole-house" source emission rates were relatively constant during both seasons, with higher rates for odorous chemicals such as p-dichlorobenzene and limonene (often used in room air fresheners) than for other classes of chemicals; (3) breath concentrations measured during morning and evening were similar for most participants, suggesting the suitability of breath measurements for estimating exposure in the home; (4) limited data obtained on two additional chemicals-toluene and methylene chloride-indicated that both were prevalent at fairly high concentrations and that indoor air concentrations exceeded outdoor concentrations by a factor of about three.

Adolescent↗

PubMed1988

Is lymphocyte magnesium concentration a reflection of intracellular magnesium concentration?

Diuretics are known to cause magnesium depletion, and the aim of the present experiment is to establish the relationship between lymphocyte magnesium concentration and intracellular magnesium concentration during chronic diuretic therapy. Studies were conducted in male Wistar rats that were subjected to daily administration of furosemide (2 mg/kg/day IP) for 19 weeks. Clearance measurements were performed during the baseline week and subsequently during the third, seventh, eleventh, fifteenth, and nineteenth weeks in both furosemide-treated (n = 32) and control rats (n = 32). Lymphocyte magnesium concentration was also measured as a determinant of intracellular magnesium concentration. Magnesium concentrations in kidney, bone, skeletal, and heart muscle tissues were also quantitated at week 11 and at the end of the experiment. After 11 weeks of furosemide administration, furosemide-treated rats developed a lower plasma magnesium concentration (0.95 +/- 0.01 mmol/L) compared with that in the control group (0.99 +/- 0.01 mmol/L). This difference persisted from week 11 to week 19 of the experiment. Fractional excretion of magnesium was modestly elevated in the furosemide-treated group. After 7 weeks of furosemide treatment, lymphocyte magnesium concentration decreased significantly in furosemide-treated rats when compared with that in the control group (1.56 +/- 0.09 micrograms/mg protein vs 1.33 +/- 0.07 micrograms/mg protein). During week 19, the lymphocyte magnesium concentration had fallen to 0.75 +/- 0.04 micrograms/mg protein as compared with 1.45 +/- 0.08 micrograms/mg protein in the control rats. There is a significant correlation between lymphocyte magnesium concentration and plasma magnesium concentration. Our present results indicate that during long-term diuretic therapy, lymphocyte magnesium concentration mirrors the reduction in plasma magnesium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Serum protein concentration and portal pressure determine the ascitic fluid protein concentration in patients with chronic liver disease.

UNLABELLED: The ascitic fluid and serum concentrations of albumin and globulin were measured simultaneously with transhepatic portal pressure determination in 56 patients with chronic liver disease to determine whether (1) portal pressure correlated with (S-Asc)A and (2) the majority of variation in ascitic fluid protein concentration between patients was related to fluid balance from serum to ascites. The mean ascitic fluid albumin concentration was 1.04 +/- 0.73 gm/dl; globulin concentration 1.31 +/- 0.80 gm/dl; and ascitic fluid total protein concentration 2.35 +/- 1.49 gm/dl. The mean serum albumin concentration was 2.58 +/- .57 gm/dl; globulin concentration 3.91 +/- .86 gm/dl; and total protein concentration 6.49 +/- 1.30 gm/dl. The (S-Asc)A was 1.54 +/- .45 gm/dl. The mean PPIVC was 14.5 +/- 4.3 mm Hg. The (S-Asc)A correlated directly with PPIVC (r = 0.73; p less than 0.0001). The ascitic fluid protein correlated with three variables that did not correlate with each other: serum albumin (r = 0.67; p less than 0.0001), serum globulin (r = 0.44; p less than 0.001), and PPIVC (r = -0.48; p less than 0.0005). The sum of the squared correlation coefficients with these latter uncorrelated variables equaled 0.87 and partial correlation coefficient analyses demonstrated an increase in the correlation of the ascitic fluid protein with the serum albumin concentration when corrected for serum globulin and (S-Asc)A (r = 0.97; p less than 0.0001) or PPIVC (r = 0.90; p less than 0.0001). Thus most of the variation in ascitic fluid protein between patients in this study could be related to serum protein concentrations and PPIVC or (S-Asc)A. Furthermore, multivariate discriminant analysis of patients with an ascitic fluid protein less than or equal to 2.5 vs. greater than 2.5 gm/dl indicated that the majority of differences between the two groups could be attributed to differences in serum albumin and serum globulin in combination with the (S-Asc)A (canonical correlation = 0.808) or PPIVC (canonical correlation = 0.806). These factors could correctly identify the low or high ascitic fluid protein groups in 96% and 93% of patients, respectively. IN CONCLUSION: (1) the (S-Asc)A is associated with the degree of portal pressure elevation and (2) the majority of variation in ascitic fluid protein concentration between patients with chronic liver disease is associated with differences in portal pressure and serum protein concentrations.

Analysis of Variance↗

PubMed1993

[Oxygen concentrators are not ozone concentrators].

Ozone is a constituent of the natural ambient atmosphere and occurs dependent on weather and environment in concentrations that can trigger airway inflammation. Oxygen concentrators are employed in oxygen long-term therapy and produce in the room air a mixture of concentrated oxygen and residual gases of unknown ozone concentration. Hence, we studied the ozone concentration of the air supplied by the oxygen concentrator, both under normal conditions in the room air and with increased ozone concentration of the air in the room. Both under room air conditions and under increased ozone concentrations of up to 12 ppm in the surrounding air the residual gas mixture of the air produced by the oxygen concentrator did not contain any ozone concentration beyond 0.005 ppm. This prompts us to suggest that the oxygen concentrators examined by use are ozone eliminators rather than ozone concentrators.

Air Pollution, Indoor↗

PubMed1999

Correlation of saliva codeine concentrations with plasma concentrations after oral codeine administration.

A clinical study was designed to determine if there was a predictable relationship between saliva and plasma codeine concentrations. Drug-free volunteers (n = 17) were administered a 30-mg dose of liquid codeine phosphate. Plasma and saliva specimens were collected at various times for 24 h after administration. Plasma and saliva were analyzed for codeine and morphine by positive-ion chemical ionization gas chromatography-mass spectrometry. The plasma codeine concentrations peaked between 30 min and 2 h after administration and ranged from 19 to 74 ng/mL with a mean of 46 ng/mL. Despite decontamination procedures, elevated saliva codeine concentrations were detected at the early collection times because of contamination of the oral cavity from the liquid codeine. Codeine concentrations in the 15 min specimens ranged from 690 ng/mL to over 15,000 ng/mL. After the initial 2-h period, the mean codeine saliva concentrations declined at a rate similar to that observed in the plasma, but remained 3 to 4 times greater than the plasma concentrations. During the elimination phase, half-life estimates for codeine in plasma and saliva were found to be equivalent, 2.6 and 2.9 h, respectively. However, the area under the curve (AUC) estimate for codeine in saliva was 13 times greater than the plasma AUC. Contamination of the saliva resulted in elevated saliva/plasma (S/P) concentration ratios for the first 1 to 2 h after drug administration. Consequently, S/P ratios in specimens collected in the first 15 to 30 min ranged from 75 to 2580. However, after the absorption phase, a significant correlation between saliva and plasma concentrations was observed (r = 0.809, p < 0.05) and mean S/P ratios remained constant (mean = 3.7). Although small changes in saliva pH were predicted to produce profound changes in the S/P ratios for codeine, this was not observed in the current study. Therefore, saliva codeine concentrations could be used to estimate plasma concentrations through the use of the S/P ratio once the oral contamination has been eliminated. However, these estimates should be made cautiously. One must ensure that oral contamination is not a factor. Also, as with blood-drug concentrations, considerable intersubject variability was observed.

Administration, Oral↗

PubMed2004

Recombinant Factor VIIa concentrate versus plasma derived concentrates for the treatment of acute bleeding episodes in people with Haemophilia A and inhibitors.

BACKGROUND: In some people with haemophilia, therapeutic clotting agents are recognised as a foreign protein and anti-FVIII antibodies, known as 'inhibitors', are produced. This review investigates which treatment most effectively arrests acute bleeding in people with haemophilia A and inhibitors. OBJECTIVES: To determine the clinical effectiveness of recombinant FVIIa concentrate in comparison to plasma-derived concentrates for the treatment of acute bleeding episodes in people with haemophilia A and inhibitors. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises of references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. Date of the most recent search of the Group's trials register: September 2003. SELECTION CRITERIA: Randomised (RCTs) and quasi-randomised controlled clinical trials comparing Recombinant FVIIa concentrate to human plasma-derived concentrates (high-dose human or recombinant FVIII concentrate; prothrombin complex concentrates (PCCs); activated prothrombin complex concentrate (aPCC)) in people with haemophilia A. Comparisons with animal derived products were excluded. DATA COLLECTION AND ANALYSIS: No studies were found that were eligible for inclusion in this review. MAIN RESULTS: A total of four studies were identified by the searches, however, none of these were eligible for inclusion in this review. REVIEWERS' CONCLUSIONS: No RCTs on the relative effectiveness of Recombinant FVIIa concentrate compared to human plasma-derived concentrates in people with haemophilia A and inhibitors were identified for inclusion in this review. The research evidence on which to base clinical decisions is therefore limited to case reports, and other less robust evidence. There is need for a well-designed, adequately-powered randomised controlled trial to assess the relative benefits and risks of using Recombinant FVIIa concentrate compared to human plasma-derived concentrates in people with haemophilia A and inhibitors.

Acute Disease↗

PubMed2000

Intrascleral concentration vs depth profile of mitomycin-C after episcleral application: impact of applied concentration and volume of mitomycin-C solution.

The purpose of this study was to investigate the impact of different concentrations and volumes of Mitomycin-C (MMC) on the intrascleral concentration vs depth profile of MMC in an experimental model. The episcleral sides of scleral quadrants of human donor eyes were exposed for 1 min to sponges (corneal light shield, Merocel Corp.) soaked with MMC. After irrigation with 40 ml saline a central 8 mm diameter scleral disk was horizontally dissected with a cryotome. MMC concentrations of six layers of 140 microns thickness were analysed by means of high-performance liquid chromatography. In Experiment 1 (11 eyes) the sponges were soaked with 50 microliters of 10, 100 and 200 micrograms ml-1 MMC solutions. In Experiment 2 (12 eyes) the sponges were soaked with 10, 30, 50 and 80 microliters of a 200 micrograms ml-1 isotonic MMC solution. In Experiment 1 the MMC concentrations (microgram g-1) of layer 1 were 0.35 (+/- 0.20; 10 micrograms ml-1 group) and 9.22 (+/- 2.92; 200 micrograms ml-1 group). In Experiment 2 the MMC concentrations were 2.57 (+/- 1.17; 10 microliters group), 7.35 (+/- 2.49; 30 microliters group) and 11.67 (+/- 3.25; 80 microliters group). The scleral MMC concentrations were significantly influenced by the applied concentrations (layers 1-5) and by the applied volumes (all layers) of MMC solution. The intrascleral MMC concentration increased linearly with increasing concentration and not linearly with increasing volume of the applied MMC solution. To achieve more predictable scleral concentrations of MMC after trabeculectomy with MMC it seems advisable to control both the concentration and the volume of the MMC solution used to soak the sponge.

Absorption↗

PubMed1991

A prospective evaluation of elevated serum theophylline concentrations to determine if high concentrations are predictable.

PURPOSE: To evaluate prospectively whether serum theophylline concentrations of 25 mg/L and greater were predictable (and presumably preventable) by use of basic pharmacokinetic calculations. DESIGN: Prospective study. PATIENTS: Fifty-five patients with a serum theophylline concentration of at least 25.0 mg/L were evaluated initially and if subsequent elevated theophylline concentrations occurred. INTERVENTIONS: The predicted steady-state serum theophylline concentration was calculated from the dosage rate divided by the predicted clearance to determine how many elevated concentrations (greater than 20 mg/L) were predictable. Predicted clearances were 0.04 L/kg/hour for normal subjects less than 70 years of age and 0.02 L/kg/hour for patients with congestive heart failure, chronic obstructive pulmonary disease, or liver disease. Estimated clearances were determined and compared with predicted clearances. If patients did not have steady-state concentrations, additional calculations were made. MAIN RESULTS: From 6,368 consecutive theophylline determinations, 69 (1.08%) samples from 55 patients were 25 mg/L or higher. Predictably high concentrations occurred in 23 of 33 (69.7%) fully evaluable cases. These concentrations occurred because of a failure to consider decreased elimination clearance from congestive heart failure, chronic obstructive pulmonary disease, or hepatic disease. Five fatalities occurred, and in two cases, theophylline appeared to contribute to the patient's death. Three other patients experienced syncope. The predicted elimination clearance of theophylline of 0.02 L/kg/hour was too high in eight patients over 70 years old with cardiac or pulmonary disease. Nursing and pharmacy oversights were identified as three patients were given two theophylline products simultaneously. CONCLUSIONS: Most elevated theophylline concentrations are predictable (and preventable) by basic pharmacokinetic calculations. Patients experiencing elevated theophylline concentrations often had comorbid conditions and were greater than 60 years of age. The dosage rate of theophylline (mg/hour) can be estimated from predicted clearance (L/kg/hour) times desired steady-state serum concentration (mg/L).

Adult↗

PubMed2000

Prebeta1-high-density lipoprotein (prebeta1-HDL) concentration can change with low-density lipoprotein-cholesterol (LDL-C) concentration independent of cholesteryl ester transfer protein (CETP).

To clarify whether prebeta1-high-density lipoprotein (prebeta1-HDL) concentration changes with low-density lipoprotein-cholesterol (LDL-C) concentration independent of cholesteryl ester transfer protein (CETP), we determined prebeta1-HDL concentration by native two-dimensional gel electrophoresis in 58 subjects with normal triglyceride and HDL-cholesterol concentrations. We also measured LDL-C and CETP concentrations. In 17 subjects, a second blood sample was taken 1-6 months after the first. We found that prebeta1-HDL concentration was positively correlated with LDL-C concentration (r=0.529, P<0.0001) and with CETP mass (r=0.398, P<0.01). In 17 patients, Deltaprebeta1-HDL was positively correlated with DeltaLDL-C (r=0.635, P<0.01), but not with DeltaCETP mass (r=0.275). In conclusion, prebeta1-HDL concentration changes with LDL-C concentration independent of CETP. These results suggest that prebeta1-HDL concentration may reflect the balance between several regulatory factors, including LDL-C and CETP concentrations.

Adult↗

PubMed1996

Down-regulation of glucose transport by elevated extracellular glucose concentrations in cultured rat aortic smooth muscle cells does not normalize intracellular glucose concentrations.

Vascular disease is a prominent complication of diabetes mellitus, and hyperglycemia has been implicated as a risk factor for the development of these vascular complications. It has previously been suggested that down-regulation of glucose transport in response to hyperglycemia might serve a protective role by decreasing intracellular glucose concentrations. In the present study, regulation of glucose transport by extracellular glucose concentrations was investigated in cultured rat vascular smooth muscle cells (VSMCs). Confluent quiescent VSMCs were exposed to medium containing either normal (5 mmol/L) or elevated (20 mmol/L) extracellular glucose concentrations for 24 hours. VSMCs exposed to elevated extracellular glucose concentrations (with or without serum) for 24 hours exhibited significant decreases in 2-deoxyglucose (2-DG) and D-glucose uptake rates. This decreased glucose transport was associated with a decrease in the Vmax of D-glucose transport without a change in KM. In the absence of serum, a decrease in the quantity of GLUT-1 transport protein at the plasma membrane was noted in cells exposed to elevated extracellular glucose concentrations for 24 hours. Intracellular glucose concentrations were estimated by using two methods, and the results revealed significantly higher intracellular glucose concentrations in the cells exposed to elevated extracellular glucose concentrations for 24 hours. These results suggest that down-regulation of glucose transport in cultured VSMCs exposed to elevated extracellular glucose concentrations for 24 hours does not occur to an extent that normalizes intracellular glucose concentrations. This prolonged increase in intracellular glucose concentrations and the potential associated toxicity may explain the increased incidence of vascular complications in patients with diabetes mellitus.

Animals↗

PubMed1980

Use of salivary concentrations in the prediction of serum caffeine and theophylline concentrations in premature infants.

Simultaneous blood and saliva samples were drawn for determination of caffeine and theophylline concentrations in 17 infants receiving caffeine or theophylline therapy for apnea of prematurity. The relationship between serum and saliva concentrations in each drug treatment group was explored using (1) regression analysis and (2) serum:saliva ratio. Significant correlations were observed between serum and salivary concentrations. Salivary concentrations approximated 76 to 80% of the serum concentrations based on the derived serum:saliva ratios. When salivary concentrations were less than 8 microgram/ml, the serum concentrations did not exceed therapeutic range and no clinical toxicity was noted. Monitoring of salivary drug concentrations as an alternative to serum drug concentrations may be useful in preterm infants on methylxanthine therapy. When salivary concentrations exceed 8 microgram/ml, serum concentrations should be determined.

Apnea↗

PubMed1996

Measurement of heparin concentration in whole blood with the Hepcon/HMS device does not agree with laboratory determination of plasma heparin concentration using a chromogenic substrate for activated factor X.

UNLABELLED: Measurement of circulating heparin concentration has been suggested to optimize anticoagulation during cardiopulmonary bypass. The Hepcon/HMS device (Medtronic HemoTec, Inc., Parker, Colo.) uses heparin/protamine titration to quantitatively determine heparin concentration. Extensive validation of this instrument is still lacking. METHODS: Agreement between heparin concentrations measured by the Hepcon/HMS system and by laboratory determination was evaluated in 16 patients undergoing cardiac operations. For laboratory determinations, plasma heparin concentration was derived from the measure of anti-Xa activity by means of chromogenic substrate technique. The Hepcon/HMS instrument and cartridges measured whole blood heparin concentration. Samples were analyzed 5 minutes after administration of heparin, 15 and 30 minutes after the start of cardiopulmonary bypass, 5 minutes after aortic unclamping, at the end of cardiopulmonary bypass, and after administration of protamine. Data were plotted and interpreted according to the method of Bland and Altman: First, a difference less than 1.4 U/ml (i.e., +/- 0.7 U/ml) was chosen as acceptable, because it would not cause major difficulties in clinical interpretation; second, the difference between the two measurement techniques was plotted against the mean of the two measures. RESULTS: The mean difference (bias) between heparin concentrations derived by the Hepcon/HMS device and those obtained by laboratory determination was as expected for measures performed on whole blood versus plasma (1.45 U/ml). Nevertheless, heparin concentrations derived by the Hepcon/HMS device may be as much as 2.76 U/ml above or 6.17 U/ml below the concentrations measured in the laboratory, differences well outside the predetermined limits of agreement and clearly unacceptable for clinical purposes. CONCLUSION: We conclude that heparin concentrations determined with the Hepcon/HMS instrument do not agree with laboratory determination of heparin concentration. Monitoring of heparin concentrations during bypass with the Hepcon/HMS device cannot be recommended.

Blood Chemical Analysis↗

PubMed1998

Fatigue during repeated eccentric-concentric and pure concentric muscle actions of the plantar flexors.

OBJECTIVE: To compare the fatigue development during pure concentric actions with eccentric-concentric actions in standardized isokinetic, open-chain conditions. DESIGN: The study was performed with measurement of muscular strength and EMG of the plantar flexors on an isokinetic dynamometer. BACKGROUND: Fatigue development on a dynamometer has mostly been studied with repeated pure concentric actions. Eccentric-concentric actions are, however, often used in normal activities. An eccentric action has an immediate effect on a following concentric action and therefore it is of interest to follow the fatigue process in repeated combined actions. METHODS: Ten healthy young women participated. The pure concentric test was performed with the same number of cycles as in the eccentric-concentric test, which was performed until exhaustion. Development of MPF and RMS of the EMG in the triceps surae, as well as work, were evaluated. RESULTS: The total amount of work was significantly higher in the eccentric-concentric test than in the pure concentric test. The work decreased similarly (32-39%) with no significant difference between the two tests. A significant decrease (12-16%) in MPF was only seen in the eccentric-concentric test. No changes in RMS were seen. CONCLUSION: The similar reductions of work seen in both tests should primarily be sought in the contractile process as such. Changes in MPF may then be viewed as a phenomenon dependent on the timing of the duty cycle. RELEVANCE: The eccentric-concentric test lead to exhaustion and showed EMG changes and should therefore be recommended when evaluating the development of fatigue in muscular performances in different groups of patients.

Journal Article↗

PubMed2003

In vitro-in vivo extrapolation: estimation of human serum concentrations of chemicals equivalent to cytotoxic concentrations in vitro.

In the present study an extrapolation model for estimating serum concentrations of chemicals equivalent to in vitro effective concentrations is developed and applied to median cytotoxic concentrations (EC(50)) determined in vitro. Nominal concentrations of a chemical in serum and in vitro are regarded as equivalent, if they result in the same aqueous concentration of the unbound form. The algorithm used is based on equilibrium distribution and requires albumin binding data, the octanol-water partition coefficient (K(ow)), and the albumin concentrations and lipid volume fractions in vitro and in serum. The chemicals studied cover wide ranges of cytotoxic potency (EC(50): 2.5-530,000 microM) and lipophilicity (logK(ow): -5 to 7). Their albumin binding characteristics have been determined by means of an in vitro cytotoxicity test as described previously. The equivalent serum concentrations of 19 of the 33 compounds investigated, having high protein binding and/or lipophilicity, were substantially higher than the EC(50)-values, by factors of 2.5-58. Prominent deviations between the equivalent nominal concentrations in serum and in vitro were largely restricted to chemicals with higher cytotoxic potency (EC(50)< or =1000 microM). The results suggest that estimates of equivalent serum concentrations based on in vitro data are robust for chemicals with low lipophilicity (logK(ow)< or =2) and low potency (EC(50)>1000 microM). With more potent chemicals or those with higher lipophilicity partitioning into lipids and/or binding to serum proteins have to be taken into account when estimating in vivo serum concentrations equivalent to in vitro effective concentrations.

3T3 Cells↗

PubMed2005

Concentrations of cholesterol oxidation products in raw, heat-processed and frozen-stored meat of broiler chickens fed diets differing in the type of fat and vitamin E concentrations.

The present study was performed to investigate the effect of dietary fat and vitamin E on concentrations of cholesterol oxidation products (COP) in broiler muscle. A total of 144 1-d-old broiler chicks were fed diets with either palm oil, soyabean oil or linseed oil and vitamin E concentrations of 20, 40 or 200 mg/kg for 35 d. COP concentrations were analysed in raw, heat-processed (180 degrees C, 20 min) and frozen-stored (-20 degrees C, 6 months) breast and thigh muscles. COP concentrations were influenced by dietary vitamin E concentration, dietary fat, treatment and type of muscle (P<0.001). Increasing the dietary vitamin E concentration generally reduced the concentration of COP. This effect was strongest in broilers fed linseed oil and weakest in broilers fed palm oil; the effect of vitamin E was also stronger in heated muscles than in raw or frozen-stored muscles. Moreover, the concentration of COP in thigh muscle was more strongly influenced by dietary vitamin E than that in breast muscle. COP concentrations in muscles were on average highest in broilers fed linseed oil and lowest in broilers fed palm oil, but the effect of the dietary fat also depended on the vitamin E concentration, the treatment and the type of muscle. In conclusion, our study shows that dietary fat and vitamin E influence the concentrations of total COP in broiler muscle. However, the effects of these factors were not only influenced by interactions between each other, but also depended on the treatment of the muscle and the type of muscle.

Animals↗