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At least 811 records · Page 45Linked to original sources
PubMed1991

Contrast echocardiography enhances tricuspid but not mitral regurgitation.

Tricuspid regurgitation refers to a systolic leak of blood between the right ventricle and right atrium, across the tricuspid valve. Doppler echocardiographic examination of large numbers of normal individuals has shown that trivial tricuspid regurgitation is extremely common. Measurement of the peak velocity of the regurgitant frequency spectrum on Doppler echocardiography is of considerable clinical importance since it may be used to calculate peak right ventricular and, consequently, peak pulmonary systolic pressure. Doppler recording of the frequency spectrum of a tricuspid regurgitation jet optimally shows a smooth, parabolic, sharply demarcated envelope. In many individuals with trivial tricuspid regurgitation, however, this frequency spectrum is incomplete and its envelope is poorly demarcated. Such inadequate signals do not allow measurement of the spectrum's peak velocity. Like other contrast agents, air-filled microspheres composed of sonicated human serum albumin enhance reflection of Doppler ultrasound and thus have the potential to enhance incomplete tricuspid regurgitation spectra. Furthermore, since sonicated albumin microspheres can cross the pulmonary circulation intact, they have the potential to enhance mitral regurgitation spectra. The purpose of our study was to investigate whether injection of sonicated albumin microspheres enhances incomplete tricuspid and mitral regurgitation frequency spectra to a diagnostic quality. Sonicated albumin microsphere injection enhanced tricuspid regurgitation spectra to optimal quality in 11 of 15 patients (73%). Microsphere injection caused a minor degree of enhancement of the mitral regurgitant spectrum in 1 patient, but did not optimize the spectra in any of 10 patients tested. Saline contrast injection optimally enhanced tricuspid regurgitation spectra in all 8 patients in whom it was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Dengue virus infection of human microvascular endothelial cells from different vascular beds promotes both common and specific functional changes.

Dengue shock syndrome (DSS), the major life threatening outcome of severe dengue disease, which occurs in some patients in the course of dengue infection, is the consequence of plasma leakage in the microvascular territories. Data from clinical and in vitro studies suggest that an inadequate immunological response is partly responsible for the pathophysiology of DSS, but few is known concerning the consequences of direct infection of endothelial cells by dengue virus per se. In this study, an attempt was made to study the response of two microvascular human cell lines originating, respectively, from liver and dermis to infection by a dengue type 2 virus, by analyzing the virus-induced modulation of functional markers. It is shown that the two microvascular cell lines exhibit both common and specific behaviors upon infection. In particular, LSEC and HMEC-1 replicate efficiently the low-passage virus and respond to infection by over-producing inflammatory mediators involved in the cross talk with circulating immune cells. However, direct infection modulates differently the cell surface expression of molecules critically involved in the interactions between endothelial and inflammatory cells. ICAM-1 and HLA-I are up regulated as a consequence of infection in LSEC whereas direct infection results in downregulation of ICAM-1 in HMEC-1. The present results show that infection of human microvascular cells by unadapted dengue virus results in both common and specific activation patterns depending likely on the tissue origin of the cells, thus suggesting that endothelia from different territories may contribute differently to the pathophysiological events in the course of dengue infection.

Dengue↗
PubMed1999

Early detection of liposome brain localization in rat experimental allergic encephalomyelitis.

Blood-brain barrier (BBB) permeability increases prior to the development of clinical signs in early-stage multiple sclerosis (MS). Detection of subtle changes would thus be helpful for diagnostic purposes and rapid therapeutic decisions before new episodes. Since multiple sclerosis and experimental allergic encephalomyelitis (EAE) have numerous common features, in particular BBB-permeability characteristics, and since we have previously shown that BBB localization is disturbed by tumors, embolism, and mannitol injection, we investigated BBB-liposome permeability in an EAE rat model. Twenty young male Lewis rats received a single intradermal inoculation of guinea-pig spinal cord. The effect of the Freund's adjuvant and spinal cord alone on brain permeability were also assessed. In order to compare solution permeability and liposome localization, radioactive liposomes and, 1 h later, 99mTc-DTPA were injected intravenously. Scintigraphic acquisitions were obtained to follow the biodistribution of radioactivity in the whole body. Each rat was subjected to a first examination before inoculation and then every two days until completion and may be considered as its own control. EAE induced a previously unreported increase in global-body permeability, probably due to inflammation. Liposome brain localization and brain/heart ratio were significantly different between normal animals and those with early-stage EAE (before appearance of clinical signs) and distinguished between different disease stages in clinically patent EAE. The index of disease progression was modified earlier than with 99mTc-DTPA injection. One explanation may be particle pick-up by circulating macrophages, which cross the BBB during this pathology. For clinical applications, experiments must be confirmed on models more reliable for human multiple sclerosis.

Animals↗
PubMed1988

Kallidin and bradykinin metabolism by isolated cerebral microvessels.

Although kinins have been reported to affect cerebral vascular tone and permeability, their actions are not potentiated by angiotensin converting enzyme inhibitors. To investigate cerebral vascular kinin metabolism, porcine cerebral microvessels were isolated by differential sieving and centrifugation and characterized by microscopic examination and marker enzyme enrichment. Purified microvessels contained a membrane-bound carboxypeptidase which hydrolyzed the C-terminal Phe-Arg bond of both kallidin and bradykinin. Hydrolysis was optimal at pH 7.0, was activated more than 300% by 0.1 mM CoCl2, and was inhibited by o-phenanthroline and the carboxypeptidase N (EC 3.4.17.3) inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MERGETPA) (IC50 = 2 microM). Conversely, inhibitors of angiotensin I converting enzyme (captopril), neutral endopeptidase (phosphoramidon), post proline cleaving enzyme (Z-Pro-prolinal), dipeptidyl(amino)peptidase IV (diprotin A) and amino-peptidase M (amastatin) had no effect. When the rates of C-terminal hydrolysis of kallidin by detergent-solubilized cerebral microvasculature were determined over a range of substrate concentrations (16.6 to 250 microM), the Km and Vmax values obtained were 26.0 +/- 3.0 microM and 14.7 +/- 1.3 nmol/min/ml (N = 4) respectively. These data suggest that a cerebral microvascular carboxypeptidase may play a role in vivo in modulating the effects of kinins on cerebral blood flow and permeability and in preventing circulating kinins from crossing the blood-brain barrier.

Animals↗
PubMed1988

Influence of maternal pneumonectomy on fetal lung growth.

This study was conducted to test the hypothesis that the compensatory growth of the maternal lung during pregnancy influences fetal lung growth, specifically the fetal lung DNA content. A left pneumonectomy (PN) was performed in pregnant albino rats at different gestation days (GD 3, 7, 9, 10, 12, 14, 16 and 18) and the rats sacrificed at GD 21. Only mothers with litter size of 9-14 fetuses were used for this study. Maternal lung growth was assessed by measuring lung weight, lung air volume and lung DNA content, and the fetal lung growth by lung DNA content. The findings were: (1) pregnancy did not influence the rate of compensatory growth of the remaining lung following PN; (2) neither thoracotomy nor PN had any effect on placental weight or DNA content; (3) lung DNA content for body weight was larger in fetuses of PN rats when PN was performed in the first half of gestation; (4) there was a direct relationship between DNA content of the fetal lung and maternal lung in PN rats; and (5) neither thoracotomy nor PN in pregnant rats influenced the maturation of the fetal lung. The results suggest that a growth factor(s), specific for lungs, is released into maternal circulation following PN, crosses the placenta and enhances the fetal lung growth without affecting its maturation.

Animals↗
PubMed1983

Serum lymphocytotoxic antibodies in neuropsychiatric lupus: a serial study.

The pathogenesis of neuropsychiatric (NP) SLE remains speculative. A relationship between circulating brain cross-reactive lymphocyte antibodies (LCA) and NP-SLE has been postulated but serial, prospective study of LCA in individual patients with SLE has rarely been performed. In the current study a group of 34 patients with SLE was analyzed using clinical, neurologic, psychiatric, and neuropsychological examinations, together with routine serological tests, to define NP-SLE. Previous history of alloimmunization was also recorded. LCA were measured by a two-stage microcytotoxicity assay against a panel of 25 normal donor B and T cells, at both 40 and 37 degrees C. LCA by this method were found in the serum of 20/34 (58%) SLE, 2/22 (9%) rheumatoid arthritis, and 3/24 (12%) antinuclear-antibody-positive chronic psychiatric patients (P less than 0.01). Analysis of LCA serially in individual SLE patients revealed: (1) No difference in B- or T-cell reactivity at either 4 or 37 degrees C, (2) no significant correlation between previous alloimmunization and the presence of LCA, (3) fluctuations in LCA associated with NP-SLE relapses or remissions, but not with therapy, in 10 patients prospectively studied. A significant positive association was found between the occurrence of single neuropsychiatric events and serial LCA determinations in 180 sera (P less than 0.000001). LCA as measured in this study appear more frequently in SLE than in controls and may indicate active NP-SLE in some patients. Further study of the pathogenic role and diagnostic value of LCA in NP-SLE, including their relationship to subtle neurocognitive changes, is proposed.

Adolescent↗
PubMed1996

Leptin enters the brain by a saturable system independent of insulin.

Leptin, or OB protein, is produced by fat cells and may regulate body weight by acting on the brain. To reach the brain, circulating leptin must cross the blood-brain barrier (BBB). Intravenously injected radioiodinated leptin (125I-leptin) had an influx constant (Ki) into brain of (5.87)10(-4) ml/g-min, a rate 20 times greater than that of labeled albumin. Unlabeled leptin inhibited the influx of 125I-leptin in a dose-dependent manner whereas unlabeled tyrosine and insulin, which have saturable transport systems, were without effect. HPLC and acid precipitation showed that the radioactivity in brain and serum represented intact 125I-leptin. About 75% of the extravascular 125I-leptin in brain completely crossed the BBB to reach brain parenchyma. Autoradiography detected uptake at the choroid plexus, arcuate nuclei of the hypothalamus, and the median eminence. Saturable transport did not occur out of the brain. The results show that leptin is transported intact from blood to brain by a saturable system.

Animals↗
PubMed1987

Metabolism of opioid peptides by cerebral microvascular aminopeptidase M.

Aminopeptidase M (EC 3.4.11.2), which can degrade low molecular weight opioid peptides, has been reported in both peripheral vasculature and in the CNS. Thus, we have studied the metabolism of opioid peptides by membrane-bound aminopeptidase M derived from cerebral microvessels of hog and rabbit. Both hog and rabbit microvessels were found to contain membrane-bound aminopeptidase M. At neutral pH, microvessels preferentially degraded low molecular weight opioid peptides by hydrolysis of the N-terminal Tyr1-Gly2 bond. Degradation was inhibited by amastatin (I50 = 0.2 microM) and bestatin (10 microM), but not by a number of other peptidase inhibitors including captopril and phosphoramidon. Rates of degradation were highest for the shorter peptides (Met5- and Leu5-enkephalin) whereas beta-endorphin was nearly completely resistant to N-terminal hydrolysis. Km values for the microvascular aminopeptidase also decreased significantly with increasing peptide length (Km = 91.3 +/- 4.9 and 28.9 +/- 3.5 microM for Met5-enkephalin and Met5-enkephalin-Arg6-Phe7, respectively). Peptides known to be present within or in close proximity to cerebral vessels (e.g., neurotensin and substance P) competitively inhibited enkephalin degradation (Ki = 20.4 +/- 2.5 and 7.9 +/- 1.6 microM, respectively). These data suggest that cerebral microvascular aminopeptidase M may play a role in vivo in modulating peptide-mediated local cerebral blood flow, and in preventing circulating enkephalins from crossing the blood-brain barrier.

Aminopeptidases↗
PubMed1990

Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results.

Myocardial contrast echocardiography has been found to be a safe and useful technique for evaluating relative changes in myocardial perfusion and delineating areas at risk. Although earlier contrast agents required direct delivery into the coronary arteries or aortic root, a new echocardiographic contrast agent, sonicated albumin microspheres (Albunex), has been found to cross the pulmonary circulation in experimental models. To determine the safety and preliminary efficacy of intravenous injections of Albunex in humans, 71 patients at three independent medical institutions underwent two-dimensional echocardiographic examination before, during and after the administration of three intravenous doses of Albunex, ranging from 0.01 to 0.12 ml/kg body weight. All patients provided a complete history and underwent physical and neurologic examination and laboratory and electrocardiographic evaluation before the injections; all evaluations (except for the history) were repeated at 2 h and 3 days after the injections of Albunex. The efficacy of the injections was qualitatively assessed by two independent blinded observers using a grading system of 0 to +3, with 0 indicating an absence of contrast effect and +3 indicating full opacification of the cavities examined. All injections were well tolerated and no serious side effects were noted in any of the patients. Irrespective of dose group, a cavity opacification greater than or equal to +2 was seen in the right ventricle in 212 (88%) of 240 injections and in the left ventricle in 151 (63%) of 240 injections as judged by the independent observers. The degree of ventricular cavity opacification appeared to be dose and concentration related.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Alcohol consumption is directly associated with circulating oxidized low-density lipoprotein.

Findings on the association of alcohol consumption and oxidation of low-density lipoprotein (LDL), which is thought to play a crucial role in the generation of atherosclerotic lesion, are inconsistent. The aim of the present study was to investigate the association of total alcohol consumption and type of alcoholic beverage with circulating plasma LDL oxidation. This cross-sectional study included data of circulating oxidized LDL (ox-LDL) from a subpopulation of 587 men and women enrolled in a population-based survey conducted in 2000 in Girona (Spain). Multivariate analysis was performed to describe the independent association of alcohol consumption and ox-LDL. Increasing alcohol consumption was associated with high in vivo ox-LDL levels in the present population. The consumption of 10 g of alcohol was associated with an increase of 2.40 U/L of ox-LDL (p = 0.002). Adjustment for dietary variables, leisure-time physical activity, educational level, smoking, LDL-cholesterol, high-density lipoprotein-cholesterol, glycemia, triglycerides, diabetes, body mass index, waist circumference, and systolic and diastolic blood pressures only slightly modified this association (p = 0.003). In this full adjusted model the consumption of 10 g of alcohol per day was associated with an increase of 2.11 U/L of ox-LDL. Consumption of wine (ml/day) was associated with increasing ox-LDL levels (p = 0.029), however, attenuated after controlling for alcohol. No significant relationship of ox-LDL with alcohol-independent consumption of wine, beer, and spirits was observed. Alcohol consumption was independently and directly associated with circulating ox-LDL in the present population.

Adult↗
PubMed2006

Peripheral T cells overexpress MIP-1alpha to enhance its transendothelial migration in Alzheimer's disease.

It is unclear how circulating T cells cross the blood-brain barrier (BBB) and participate in the inflammation process in Alzheimer's disease (AD). Here we showed significantly higher macrophage inflammatory protein-1alpha (MIP-1alpha) expression in peripheral T lymphocytes of AD patients than age-matched controls. T cells crossing of the human brain microvascular endothelial cells (HBMECs) which constitute the BBB, were almost completely abrogated by anti-MIP-1alpha antibody. MIP-1alpha induced the expression of CCR5, a potential MIP-1alpha receptor, on HBMECs. HBMECs tranfected with CCR5 resulted in increased T cells transendothelial migration. CCR5 antagonist (2D7 mAb) blocked the T cells transmigration. The MIP-1alpha-CCR5 interaction promoted T cells transendothelial migration via ROCK (Rho kinase). Furthermore, Abeta injection into rats' hippocampus induced MIP-1alpha overexpression accompanied with increased T lymphocytes occurrence in the brain cortex and this enhanced T cells entry was effectively blocked by anti-MIP-1alpha antibody. These data are the first to suggest that the interaction between MIP-1alpha overexpressed by T cells and CCR5 on HBMECs is involved in AD patients' T cells migrating from blood to brain.

Aged↗
PubMedDate not supplied

Assessment of myocardial perfusion with real-time myocardial contrast echocardiography: methodology and clinical applications.

Real-time myocardial contrast perfusion imaging (RTMCI) with echocardiography is a promising technique for evaluation of patients with known or suspected coronary artery disease. The technique is based on the utilization of small (<10 mum) microbubbles, which are capable of crossing the pulmonary circulation after intravenous injection. Unlike radioactive isotopes, which are taken actively or diffuse passively in the myocytes, myocardial contrast agents remain extracellularly in the capillaries and present a measure of the myocardial capillary blood volume and microvascular integrity. RTMCI has been shown to be a safe and feasible method for the assessment of myocardial perfusion at rest and with pharmacologic stress. Recent studies have shown the value of RTMCI with dobutamine stress in improving overall and regional detection of coronary artery disease and detecting of abnormalities at submaximal stress, therefore improving sensitivity in patients who are unable to achieve the target heart rate. The advantages of the technique include the ability to assess perfusion at bedside in one setting, simultaneous assessment of myocardial function, shorter imaging time, no need for ionizing irradiation, immediate availability of the results, and the ability to determine the ischemic threshold. Recent studies have shown that RTMCI improves the prognostic utility of standard dobutamine stress in addition to wall motion analysis. Patients with normal perfusion had a better outcome than those with normal wall motion. The combination of abnormal wall motion and perfusion identified patients at greatest risk of death and nonfatal myocardial infarction. Perfusion abnormalities were also shown to predict short-term cardiac events in patients presenting to the emergency department with chest pain and no ST-segment elevation. Refinement of imaging techniques is expected to improve the specificity of RTMCI, particularly in differentiating true perfusion defects from artifacts. This review will discuss the physiologic basis, methodology, clinical utility, and limitations of RTMCI in the assessment of patients with known or suspected coronary artery disease.

Computer Systems↗
PubMedDate not supplied

Peptide neurotoxins, small-cell lung carcinoma andneurological paraneoplastic syndromes.

Peptide neurotoxins isolated from the venom of snakes, spiders and snails have represented invaluable tools for the identification and characterisation of membrane ion channels and receptors in vertebrate cells, including human neurons. We here report on the use of these toxins for the characterisation of membrane ion channels and receptors expressed by one of the most aggressive human cancers, small-cell lung carcinoma. This tumour shares many properties with other neuro-endocrine cell types, including the ability of firing action potentials and release hormones in a calcium-dependent manner. Toxins such as alpha-bungarotoxin and omega-conotoxins, among others, have been successfully used to characterise neuronal nicotinic receptors and voltage-dependent calcium channels, respectively, in human small-cell lung carcinoma cells. These receptors and ion channels are not only crucial for the growth of this specific tumour, but also represent autoantigens against which cancer patients build an autoimmune response. Although the aim of this autoimmune response is eventually the destruction of the cancer cells, the circulating antibodies cross-react with similar ion channels and receptors present in normal neurons or other cells, causing a number of different paraneoplastic diseases, the best characterised of which is the Lambert-Eaton myasthenic syndrome. Conotoxin-based radioimmunoassays have become an invaluable tool for the diagnosis and follow up of these paraneoplastic disorders and could represent a step forward in the early diagnosis of small-cell lung carcinoma itself.

Binding Sites↗
PubMed2001

Studies on the role of the minor capsid protein in transport of Beet western yellows virus through Myzus persicae.

Beet western yellows virus (BWYV), family Luteoviridae, is an icosahedral plant virus which is strictly transmitted by aphids in a persistent and circulative manner. Virions cross two cellular barriers in the aphid by receptor-based mechanisms involving endocytosis and exocytosis. Particles are first transported across intestinal cells into the haemolymph and then across accessory salivary gland cells for delivery to the plant via saliva. We identified the midgut part of the digestive tract as the site of intestinal passage by BWYV virions. To analyse the role in transmission of the minor capsid component, the readthrough (RT) protein, the fate of a BWYV RT-deficient non-transmissible mutant was followed by transmission electron microscopy in the vector Myzus persicae. This mutant was observed in the gut lumen but was never found inside midgut cells. However, virion aggregates were detected in the basal lamina of midgut cells when BWYV antiserum was microinjected into the haemolymph. The presence of virions in the haemolymph was confirmed by a sensitive molecular technique for detecting viral RNA. Thus, transport of the mutant virions through intestinal cells occurred but at a low frequency. Even when microinjected into the haemolymph, the RT protein mutant was never detected near or in the accessory salivary gland cells. We conclude that the RT protein is not strictly required for the transport of virus particles through midgut cells, but is necessary for the maintenance of virions in the haemolymph and their passage through accessory salivary gland cells.

Animals↗
PubMed2002

Altered vascular function in healthy normotensive pregnant women with bilateral uterine artery notches.

OBJECTIVES: To assess endothelial function and vascular mechanical properties in normotensive pregnant women with high resistance in the uteroplacental circulation. DESIGN: Cross-sectional prospective study. SETTING: Doppler ultrasound laboratory at university department of obstetrics and gynaecology referral centre for high risk pregnancies. PARTICIPANTS: Forty-two caucasian normotensive pregnant women: 23 with uncomplicated pregnancies and 19 with bilateral uterine artery notches. METHODS: Flow-mediated dilatation of the brachial artery was measured by ultrasonography at 25 gestational weeks. Concentrations of nitrite and nitrate in the plasma were established at 25 and 32 gestational weeks. The elastic properties of the common carotid artery, abdominal aorta and popliteal artery were measured with an ultrasonic echo-tracking system. RESULTS: Flow-mediated dilatation at two minutes after cuff deflation was significantly lower in the bilateral notch group compared with the control group, 8.3% and 13.7%, respectively (P = 0.0007). The ability to sustain vasodilatation was reduced in the bilateral notch group (P = 0.02). Lower values of nitrite and nitrate in the plasma were found at 32 gestational weeks in the bilateral notch group than in the control group (mean 24.76 microM/L (SD 5.6) and 30.93 microM/L (8.2), respectively; P = 0.008). Nitrite and nitrate levels tended to be lower in the bilateral notch group even at 25 gestational weeks (29.45 microM/L (8.3) and 35.73 microM/L (11.0) in the bilateral notch and control group, respectively; P = 0.09). There was no difference in aortic, carotid or popliteal elasticity between the two groups. CONCLUSIONS: Healthy normotensive pregnant women with bilateral uterine artery notches show impaired endothelial function, but no differences in vascular mechanical properties.

Arteries↗
PubMed1995

Left atrial-aortic/femoral bypass with a centrifugal pump without systemic heparin during surgery on the descending aorta.

Active or passive bypass to support the distal circulation during cross-clamping of the descending thoracic aorta has been reported to decrease the incidence of paraparesis, to reduce left ventricle afterload, and to preserve distal organ perfusion. The aim of this study was to describe and to evaluate a perfusion technique for surgery on the descending aorta in humans. Nine patients underwent surgery on the descending thoracic aorta. The left atrium was cannulated using a Carmeda bioactive surface cannula. Distal cannulation sites were the left common femoral artery or the aorta below the involved segment. The cannulae were connected to a BioMedicus centrifugal pump via Carmeda bioactive surface tubings and pump heads. No systemic heparin was used. Cross-clamp time was 51 +/- 6 min, and the pump flow was 2.3 +/- 0.2 L/min. The mean arterial pressure in the upper body was 81 +/- 4 mm Hg and 68 +/- 5 mm Hg in the lower. Seven patients were discharged from hospital. Two patients with aortic rupture died; one died on the operating table, and the other, neurologically intact, died 4 days postoperatively due to multiorgan failure. No patients suffered spinal cord injury. It is concluded that active bypass without systemic heparin during cross-clamping of the descending aorta is simple and safe.

Adult↗
PubMed2001

Age-dependent presence of antibodies in rat dams, capable of conferring protection against group B Streptococcus infection in neonates.

A rat model was used to investigate maternal age-dependent resistance on group B Streptococcus (GBS)-induced mortality of the offspring. Offspring from young (first time) or older (repeat litters) dams were challenged with GBS. There was an approximate log difference in the dose of GBS required to cause identical levels of mortality in the two groups. The sera of the dams from both groups were analysed by whole-cell ELISA, and it was demonstrated that sera from the older dams possessed circulating IgG cross-reactive to GBS. Since IgG is transplacentally transferred, we conclude that this is the method of observed protection.

Aging↗
PubMed1979

Methotrexate concentrations in biological fluids: comparison of results obtained by radioimmunoassay and direct ligand binding radioassay.

A sensitive (sensitivity 2.2 X 10(-9) mol/l) and specific (practically no cross-reaction with circulating folates) radioimmunoassay for the determination of methotrexate concentrations in biological fluids in described and compared with a commercial competitive protein binding assay. Antiserum with high titer was produced in rabbits immunized with MTX-human serum albumin conjugate. Fitness for use in pharmacokinetic drug level determinations was shown in three patients, who received both low doses and high dose therapy combined with citrovorum factor rescue. An excellent correlation was found between plasma and urine MTX concentrations obtained by RIA and competitive protein binding assay. A two-compartment pharmacokinetic model was found adequately describing the serum decay curves, but there was a great interindividual variability in the calculated pharmacokinetic parameters.

Adult↗