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BACKGROUND: The aim of this paper was to validate an inductively coupled plasma-mass spectrometry (ICP-MS) method to quantify tungsten in human plasma and to study its percentage binding to plasma proteins. METHODS: This method was validated with respect to accuracy, precision, selectivity and limits of quantification and of detection according to Good Laboratory Practice Guidelines. Calibration curves were obtained in the range 10-500 ng/ml. The extent of plasma protein binding was determined by ultrafiltration in the range 40-2000 ng/ml. RESULTS: A significant matrix effect was observed. The linearity of this method was statistically proven. Precision ranged from 0.76% to 6.49%, and accuracy from 97% to 102%. The lower limit of quantification (LLOQ) was 10 ng/ml. The mean percentage of unbound fraction was 89%. CONCLUSIONS: The results obtained indicate that the method described fulfills the accuracy and precision requirements necessary to carry out pharmacokinetic studies in man.
Leptin, the satiety hormone expressed almost exclusively in adipose tissue, is a marker of body fat accumulation in humans. Recent studies have shown that plasminogen activator inhibitor-1 (PAI-1), a prothrombotic factor associated with atherosclerosis complications, is also produced in adipose tissue. The objective of the present study was to determine whether PAI-1 antigen plasma concentrations are associated with leptin plasma levels or the body fat mass (FM) independently of the variables known to influence PAI-1 production. Sixty-one nondiabetic women aged 18 to 45 years with a wide range of values for the body mass index ([BMI] 18.1 to 37.7 kg/m2) were evaluated for (1) body FM and fasting plasma levels of (2) PAI-1 antigen, (3) PAI-1 activity, (4) leptin, (5) insulin, (6) blood glucose, and (7) lipids (cholesterol, high-density lipoprotein [HDL]-cholesterol, and triglycerides [TG]). Body FM and fat-free mass (FFM) were estimated during fasting conditions by the bioimpedance analysis (BIA) method using a tetrapolar device. Body fat distribution was evaluated by the waist circumference and the waist to hip ratio (WHR). FM was directly associated with both PAI-1 antigen (r = .585, P < .001) and PAI-1 activity (r = .339, P < .001). Seemingly, leptin was positively related to both PAI-1 antigen (r = .630, P < .001) and PAI-1 activity (r = .497, P < .001). Moreover, both PAI-I antigen and PAI-1 activity were directly correlated with FFM (r = .285, P < .05, and r = .336, P < .01, respectively), BMI (r = .594, P < .001, and r = .458, P < .001, respectively), and WHR (r = .510, P < .001, and r = .391, P < .005, respectively). Insulin was directly related to PAI-1 antigen (r = .540, P < .001), PAI-1 activity (r = .259, P < .05), leptin (r = .447, P < .001), and FM (r = .435, P < .001). The association between PAI-1 antigen (dependent variable) and leptin or FM was tested by a stepwise regression model simultaneously including leptin, FM, BMI, WHR, age, FFM, and fasting insulin, blood glucose, TG, cholesterol, and HDL-cholesterol as independent variables. PAI-1 antigen maintained a significant positive independent relationship only with leptin (t = 2.923, P < .01), insulin (t = 3.489, P < .001), and fasting blood glucose (t = 2.092, P < .05), and a negative independent relationship with HDL-cholesterol (t = -2.634, P < .05). In conclusion, the strong relationship between PAI-1 antigen and leptin irrespective of other variables known to influence these factors seems to indicate that leptin per se may potentially increase PAI-1 plasma concentrations in obese subjects.
In order to investigate the role of renin secretion and of ACTH on the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), plasma cortisol (PC) and PA were determined at short-time intervals in 10 normal supine men. Six subjects were studied under a normal sodium intake and 4 under sodium restriction. In 4 subjects the secretion of ACTH was suppressed by dexamethasone. Under normal sodium intake changes in PA seemed to be more in parallel with changes in PC than by those in PRA as indicated by a higher significant correlation between PA and PC than between PA and PRA in 3 of the 4 subjects. In 1 subject no correlation was observed between PA and PC despite visual synchronism between the plasma concentrations of both hormones. Under dexamethasone medication fluctuations in PA were followed by those in PRA while PC was less than 2 mug/100 ml. In the sodium restricted state, changes in PA were closely paralleled and significantly correlated to PRA while no correlation was seen between PA and PC. Under dexamethasone medication the significant correlation between PA and PRA persisted. Our results indicate that in normal supine man the influence of ACTH and renin on PA may vary with different sodium intakes. Under normal sodium intake ACTH seems to be the dominant factor controlling PA, whereas under sodium restriction changes in PA are mediated through the renin angiotensin system. When the secretion of ACTH is suppressed by dexamethasone, renin controls PA both under normal and low sodium intake.
BACKGROUND: The objective of this study is the prevention of unexpected hypotension during hemodialysis caused by unsuitable filtration rate. METHODS: The plasma colloidal osmotic pressure (COP) was measured continuously during ultra-filtration, and relative plasma volume (%PV) and plasma refilling rate (PRR) were calculated during 12 ECUMs and one dialysis on twelve patients in early stage of chronic renal failure. Values of %PV and PRR calculated from COP were drawn in graphic curves, and analysed to obtain characteristic pattern. Minimum value of %PV (%PV min), maximum value of PRR (PRRmax) and time for PRR to decrease to 95% (95% PVt) on the curves were documented simultaneously. RESULTS: At the initial stage of %PV curve, obvious fall was observed on 6 of 13 estimation (initial fall of %PV). On the contrary at the initial stage of PRR curve, obvious rise was observed on 5 estimation (initial rise of PRR). A close relationship was indicated between the two phenomenons. In 6 cases with initial fall of %PV and in 5 cases with initial rise of PRR body weight, PRRmax and 95%PVt were lower than another cases without it. The ultra-infiltration velocity was estimated to be relatively high in these groups. In these 8 cases, filtrated water volume was judged as adequate clinically. In 4 of 5 cases without final fall of PRR, it was judged as inadequate and needed to evacuate more 0.9 to 3.0 kg (average of 1.8 +/- 1.07) of water from the patients. CONCLUSIONS: From the above, we concluded that our method is useful for deciding suitable velocity of ultrafiltration and dry weight in hemodialysis therapy.)
Numerous simplified methods for the estimation of ERPF have described, including the so-called slope/intercept (SI) methods, based on the analysis of the slope of certain segments of the 131I-OIH plasma disappearance curve and its y-axis intercept, and the single sample (SS) clearance method, based on theoretical volumes of OIH distribution at some fixed time after injection. Using ERPFs estimated from compartment analysis of the entire 60-min plasma disappearance curve, we have compared the errors of data calculated from use of eight SI methods made at various times along the disappearance curve with that from the optimum SS curve. The errors obtained from the SS method were approximately 50% less than those obtained from the SI methods. The errors of the SI methods are greater at both ends of the 60-min plasma curve than when samples are drawn near the mid-time. The SS method appears to be the method of choice for the estimation of ERPF using single injection techniques.
To understand the role of human cholesteryl ester transfer protein (CETP) in plasma lipoprotein metabolism, CETP activity and mass levels, lipoprotein and apolipoprotein concentrations, and the size of high-density lipoprotein (HDL) were determined in 15 heterozygotes and compared with those of four homozygotes and 20 normolipidemic controls. Plasma CETP activity and mass were totally deficient in the four homozygotes for CETP deficiency, while heterozygotes had approximately half the level of normals. CETP activity positively correlated with CETP mass levels (r = .95, P less than .001). No significant difference was observed in the level of low-density lipoprotein (LDL)-cholesterol among the three groups. The concentration of HDL2-cholesterol in the heterozygotes was approximately twice as high as that in controls, while that of homozygotes was sixfold higher than that in controls. No significant difference in the HDL3-cholesterol level was observed among the three groups. The HDL2-cholesterol to HDL3-cholesterol ratio of homozygotes was sixfold higher than that of controls, while heterozygotes showed intermediate values between homozygotes and controls. Negative correlations were found between CETP activity and HDL2-cholesterol level (r = -.884, P less than .001) and between CETP mass and HDL2-cholesterol level (r = -.829, P less than .001). Plasma apolipoprotein (apo) A-I, C-III, and E were markedly increased in homozygotes, but the differences between normal and heterozygotes were not statistically significant. The HDL size of homozygotes, determined by high-performance liquid chromatography (HPLC), was large, whereas that of heterozygotes was intermediate between homozygotes and normals.(ABSTRACT TRUNCATED AT 250 WORDS)
We studied the effects of furosemide on plasma renin and plasma aldosterone in 8 patients with mild to moderate congestive heart failure. In particular, we tried to correlate these effects with changes in plasma electrolyte concentrations and with the diuretic response on furosemide. We concluded that the diuretic response in patients with congestive heart failure is not dependent on the initial serum renin nor on the initial serum aldosterone concentration. The diuretic response did not correlate either with the changes in serum renin and/or serum aldosterone concentration. Serum renin and serum aldosterone correlated mutually before and after intravenous furosemide. We confirmed the inverse correlation between serum sodium and serum renin. SeNa and SeK correlated at all times with serum aldosterone; SeCl correlated with serum aldosterone only before intravenous furosemide administration. Indirect evidence could be provided that in patients with congestive heart failure a decreased renal blood flow is present, using the urinary beta 2-microglobulin concentration. Aldosterone has again, indirectly, proved to be integrated in the renal magnesium handling.
The effects of endogenous Plasma Renin Substrate (PRS) on the relationship between Plasma Renin Activity (PRA) and the Plasma Renin Concentration (PRC) have been studied in hyperthyroid rats, by I-triiodothyronine (T3) administration and in hypothyroid rats, by propylthiouracil (PTU) treatment, to clarify if PRA changes are an adequate index for evaluating the renin-angiotensin changes during the alterations in the thyroid function. Although in experimental situations studied the induced variation on PRC explains a 62 per cent of the changes in PRA, finding a good lineal correlation between both parameters (r = 0.79, P less than 0.001). Not only does PRS play an important role on the kinetic of the enzymatic reaction but also explains jointly with PRC up to a 85 per cent of PRA alterations. PRS changes become more important during thyrotoxicosis where they limit in a higher degree the velocity of reaction due to inverse relationship between PRC and PRS (r = 0.74, P less than 0.001).
The diurnal rhythm of plasma aldosterone concentration (PA), plasma renin activity (PRA), plasma cortisol (PC) and serum growth hormone (GH) were examined in 5 cases of normotensive acromegaly and the results were compared with the observations in normal subjects. Moreover, the response of PA to angiotensin-II infusion was studied in 6 cases of normotensive acromegaly. A normal diurnal rhythm with the lowest values in the evening or midnight and the highest values in the morning was observed in 3 of 5 cases in PA and 3 of 4 cases in PC. On the other hand, no apparent rhythm of GH was observed in any cases and that of PRA in 4 of 5 cases. Although there was a significant positive correlation between PA and PC, no significant correlation was demonstrated between PA and PRA. The response of PA to angiotensin-II fusion was significantly suppressed in normotensive acromegaly as compared to the normal subjects in spite of normal levels of PRA except for 1 case. The above observations were interpreted to suggest that the aldosterone regulation system is slightly altered in a certain number of patients with normotensive acromegaly in contrast to the normal subjects in which PRA is the main contributing factor. The low PA and suppressed response of PA toangiotensin-II infusion may suggest the defective action of angiotensin-II infusion on the adrenal gland.
Two procedures are now used in France to reduce the risk of viral transmission by blood plasma transfusion: either a quarantine method or a chemical method based on solvent-detergent technic. Since August 4th, 1992, a chemical virus inactivated blood plasma product from the Bordeaux blood bank has been authorized.
The etiology of hepatorenal syndrome (HRS) is still incompletely understood, but the atriopeptin-renin-aldosterone system plays an important role in its pathogenesis. Since this system presents a circadian rhythmicity, the aim of the study was to investigate the circadian rhythm in the circulating concentrations of atriopeptin (atrial natriuretic peptide, pANP), plasma renin activity (PRA) and plasma aldosterone (pA) in patients with HRS, compared with healthy controls. Venous blood samples were drawn during the span of a whole day and every two hours from a peripheral vein in 10 healthy subjects and in 10 patients with HRS. The circulating concentrations of pANP, PRA and pA were determined by radioimmunoassay. Statistical analysis was carried out by the "cosinor" method. The controls presented a significant (p < 0.05) circadian rhythm for each variable, whereas no rhythm (p > 0.05) was found in HRS patients. The pANP, PRA and pA rhythms were significantly (p < 0.05) different between the two groups, HRS patients having higher mean daily concentrations and larger circadian variations of pANP, PRA and pA than controls. Significant relations (p < 0.05) were demonstrated between the mean daily concentrations of pANP and PRA (r = 0.79), PRA and pA (r = 0.73) and PRA and pA (r = 0.76) in the controls; on the contrary, the HRS patients showed only a significant (p < 0.05) positive relation between pANP and PRA (r = 0.71). These results confirm the previous observation that the atriopeptin-renin- aldosterone system presents a well-defined circadian time structure in healthy subjects, while the HRS patients present a complete loss of the secretory sequentiality and of the circadian rhythm, with desynchronization of the whole system. This great upset in the temporal and functional organizations of the system could play an important role in promoting and/or in maintaining the hydro-electrolyte unbalance of HRS.
Blood collected into different anticoagulants was stored in small tubes at +4 degrees C for up to 26 h. Seven blood coagulation analyses were performed under standardized conditions. High yield and stability of factor VIII:C were found for ACD and CPD-adenine. No changes could be found in the other six parameters tested. Whole blood in blood bags could be stored for 2-4 h at +4 degrees C with maximal yield of F VIII:C, with blood stored overnight the recovery was 65%. In plasma F VIII:C was stable for at least 2 h at room temperature. F VIIIR:Ag and F VIIIR:RCoF were stable in both whole blood and plasma. No activation by plasmin as measured by B beta 15-42 could be demonstrated. The initial FPA levels, reflecting thrombin activation, in the donated blood differed individually and in some blood bags very high concentrations were found. The levels of FPA were not correlated to the time for collection of a bag of blood.
The activity inducing PMN aggregation, the chemotactic activity, and the activity augmenting PMN adherence were estimated in plasma of 40 untreated patients with Hodgkin's disease. The first two activities were evident in all patients with advanced clinical stages (III and IV). It seems to be the result of disseminated intravascular complement activation due to the circulating immune complexes. The plasma activity augmenting PMN adherence was similarly noticed, except for 1, in patients with advanced stages of the disease, but only when the general symptoms were present. Our results, if confirmed, might be helpful in improving clinical staging of patients with Hodgkin's disease.
BACKGROUND: Guillain-Barré syndrome is an acute symmetric usually ascending and usually paralysing illness due to inflammation of peripheral nerves. It is thought to be caused by autoimmune factors, such as antibodies. Plasma exchange removes antibodies and other potentially injurious factors from the blood stream. It involves connecting the patient's blood circulation to a machine which exchanges the plasma for a substitute solution, usually albumin. Several studies have evaluated plasma exchange for Guillain-Barré syndrome. OBJECTIVES: To systematically review the evidence concerning the efficacy of plasma exchange for treating Guillain-Barré syndrome. SEARCH STRATEGY: Search of the Cochrane Neuromuscular Disease Trial Register for randomised trials concerning plasma exchange in Guillain-Barré syndrome, search of the bibliographies of identified papers and enquiry from the authors of the papers. SELECTION CRITERIA: Randomised and quasi-randomised trials of plasma exchange versus sham exchange or supportive treatment. DATA COLLECTION AND ANALYSIS: Potentially relevant papers were scrutinised by two reviewers and the selection of eligible studies was agreed by them and a third reviewer. Data were extracted by one reviewer and checked by a second reviewer. Some missing data were obtained from the authors of studies. MAIN RESULTS: Six eligible trials concerning 649 patients were identified, all comparing plasma exchange versus supportive treatment alone. Primary outcome measures ~Bullet~Time to recover walking with aid In the only two trials for which this measure was reported the median time to recover this ability was faster in the plasma exchange than the control group. ~Bullet~Time to onset of motor recovery in mildly affected patients In the one trial for which this measure was available the time was significantly shortened in the plasma exchange group. Secondary outcome measures ~Bullet~Improvement in disability grade at 4 weeks In five trials, there were significantly more patients who had improved by one disability grade or more in the plasma exchange group as compared to the control group. Patients treated with plasma exchange fared significantly better in the following secondary outcome measures: time to recover walking without aid, percentage of patients requiring artificial ventilation, duration of ventilation, full muscle strength recovery after one year, and severe sequelae after one year. There were less patients with infectious events and cardiac arrhythmias in the plasma exchange than the control group. Subgroup analyses Plasma exchange was beneficial in patients with mild, moderate and severe (needing ventilation) Guillain-Barré syndrome. It was beneficial in patients with a disease duration of seven or less days and also in those with disease lasting more than seven days. However, in the only trial that enrolled patients up to 30 days from disease onset, the benefit of plasma exchange in patients treated after seven days was less apparent. Type of treatment Single studies showed that two plasma exchanges were significantly superior to none for mild Guillain-Barré syndrome and four to two for moderate Guillain-Barré syndrome but that six were not superior to four for severe Guillain-Barré syndrome requiring ventilation. One study suggested that continuous flow plasma exchange was significantly superior to intermittent flow. Another study found no significant difference between the two techniques. The same study found a significantly higher rate of adverse events with fresh frozen plasma as the replacement fluid than albumin. REVIEWER'S CONCLUSIONS: Plasma exchange is the first and only treatment that has been proven to be superior to supportive treatment alone in Guillain-Barré syndrome. Consequently, plasma exchange should be regarded as the treatment against which new treatments, such as intravenous immunoglobulin, should be judged. In mild Guillain-Barré syndrome two sessions of plasma exchange are superior to none. In moderate Guillain-Barré syndrome four sessions are superior to two. In severe Guillain-Barré syndrome six sessions are no better than four. Continuous flow plasma exchange machines may be superior to intermittent flow machines and albumin to fresh frozen plasma as the exchange fluid. Plasma exchange is more beneficial when started within seven days after disease onset rather than later, but was still beneficial in patients treated up to 30 days after disease onset. The value of plasma exchange in children less than 12 years old is not known.
Transthyretin and retinol-binding protein are sensitive markers of acute protein-calorie malnutrition both for early diagnosis and dietary evaluation. A preliminary study showed that retinol-binding protein is the most sensitive marker of protein-calorie malnutrition in cirrhotic patients, even those with the mild form of the disease (Child A). However, in addition to being affected by protein-calorie malnutrition, the levels of these short half-life-liver-produced proteins are also influenced by other factors of a nutritional (zinc, tryptophan, vitamin A, etc) and non-nutritional (sex, aging, hormones, renal and liver functions and inflammatory activity) nature. These interactions were investigated in 11 adult male patients (49.9 +/- 9.2 years of age) with alcoholic cirrhosis (Child-Pugh grade A) and with normal renal function. Both transthyretin and retinol binding protein were reduced below normal levels in 55% of the patients, in close agreement with their plasma levels of retinol. In 67% of the patients (4/6), the reduced levels of transthyretin and retinol-binding protein were caused by altered liver function and in 50% (3/6) they were caused by protein-calorie malnutrition. Thus, the present data, taken as a whole, indicate that reduced transthyretin and retinol-binding protein levels in mild cirrhosis of the liver are mainly due to liver failure and/or vitamin A status rather than representing an isolated protein-calorie malnutrition indicator.
A previous investigation suggested that the use of plasma as the biological fluid for measurement of amphotericin B (AmpB) concentrations greatly underestimates the concentrations of AmpB in the total blood circulation following amphotericin B lipid complex (ABLC) administration to humans. The purpose of this study was to determine if differences in the method used to obtain plasma from whole blood influences the percentage of AmpB recovered in plasma following ABLC incubation in whole blood. ABLC (5 microg AmpB/ml; peak blood concentration observed in rabbits following intravenous bolus of ABLC at a dose of 1 mg/kg) was incubated in whole blood for 5 min at 25 degrees C. These conditions were used to mimic the sample retrieval conditions used when blood is obtained from animals and human patients. Following incubation, plasma was obtained from whole blood using five different methods: (A) Whole blood was centrifuged for 5 min at 23 degrees C, and the plasma was separated; (B) whole blood was stored at 4 degrees C for 18 h, and the plasma was separated by gravity; (C) whole blood was stored at 23 degrees C for 18h, and the plasma was separated by gravity; (D) whole blood was stored at 37 degrees C for 18 h in a water bath, and the plasma was separated by gravity; and (E) whole blood was stored at 30 degrees C for 18 h in a water bath, and the plasma was separated by gravity. All samples were protectedfrom light throughout the duration of the experiment. AmpB concentration in each plasma sample was determined by high-performance liquid chromatography (HPLC) using an external calibration curve. The whole blood:plasma Amp B concentration ratio and the percentage of AmpB partitioned into plasma following incubation of ABLC in whole blood for each plasma separation procedure was as follows: (A) 6.5:1 blood:plasma AmpB concentration ratio, 15.4% +/- 1.6% AmpB in plasma; (B) 2.98:1 blood:plasma AmpB concentration ratio, 33.6% +/- 7.7% AmpB in plasma; (C) 1.5:1 blood:plasma AmpB concentration ratio, 67.6% +/- 10.3% AmpB in plasma; (D) 1.5:1 blood : plasma concentration ratio, 68.1% +/- 1.1% AmpB in plasma; and (E) 1.2 : 1 blood:plasma AmpB concentration ratio; 83.4% +/- 5.5% AmpB in plasma. These findings suggest that when measurement of AmpB in plasma is required following ABLC administration, incubation of whole blood at 30 degrees C for 18 h appears to be the most effective method.