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Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion.

The activity of dihydropyrimidine dehydrogenase (DPD) in peripheral blood mononuclear cells and plasma concentration of 5-fluorouracil (FUra) were simultaneously determined in cancer patients receiving FUra by protracted continuous infusion (300 mg/m2/day). Blood samples were drawn every 3 h over 24-h period and the resulting DPD and FUra values analyzed for circadian periodicity. In the seven patients studied, a circadian rhythm of DPD activity was observed (P less than 0.00001, Cosinor analysis) with the peak of activity at 1 a.m. (0.197 +/- 0.007 nmol/min/mg) and the trough at a 1 p.m. (0.113 +/- 0.007 nmol/min/mg). In addition, a circadian rhythm was observed for the plasma concentrations of FUra obtained over a 24-h period (P less than 0.00001, Cosinor analysis) with peak values (27.4 +/- 1.3 ng/ml) occurring at 11 a.m. and trough values (5.6 +/- 1.3 ng/ml) occurring at 11 p.m. The ratio of the maximum concentration of FUra to the minimum concentration observed was almost 5-fold. This study demonstrates a circadian variation of DPD activity in human peripheral blood mononuclear cells and a circadian variation of FUra plasma levels in patients receiving FUra by protracted continuous infusion. An inverse relationship between the circadian patterns of DPD activity and FUra plasma levels was also noted, suggesting that an association may exist between DPD activity and FUra plasma concentration. Further evidence of an association between DPD activity in peripheral blood mononuclear cells and plasma FUra concentration was demonstrated by a linear relationship between the two parameters in all patients (r = -0.627) and within individual patients (-0.978 less than r less than -0.742). With the recent advent of programmable pumps, information on the circadian pattern of FUra and/or DPD may be useful in planning continuous infusion schedules in order that optimal plasma drug concentration may be maintained over a 24-h cycle, thereby enhancing the therapeutic efficacy of FUra administered by continuous infusion.

Aged↗

Apolipoprotein B-100 of plasma low density lipoproteins undergoes proteolysis by contact activation factors when plasma is treated with dextran sulfate-500-MgCl2.

Human plasma low density lipoproteins (LDL) isolated by ultracentrifugation showed a single band corresponding to apolipoprotein B-100 (apoB-100) by SDS-gradient gel electrophoresis (GGE). In turn, apoB-100 of LDL precipitated from plasma by dextran sulfate-500 (DS)-MgCl2 exhibited several bands indicative of a degradative process. The degradation was more extensive at 0 degrees C than at either 23 degrees C or 37 degrees C, and appeared to be related to a protease activity that cleaved both the synthetic peptide, Z-Phe-Arg-7-amido-4-methylcoumarin (Z-Phe-Arg-AMC) and apoB-100. Proteolysis was proportional to the DS added to the plasma, was prevented by the kallikrein inhibitor, D-Phe-L-Phe-L-Arg-CHCl2, and was significantly decreased in plasma specimens of patients with either factor XII or prekalikrein deficiency. LDL pre-purified by ultracentrifugation and then precipitated by DS in the absence of plasma exhibited no proteolysis. However, proteolysis was observed when LDL interacted with kallikrein. The two main apolipoproteins of HDL3, apoA-I and apoA-II, were not affected by this proteolytic process. We interpret the results to indicate that the negatively charged surface provided by DS accelerates in plasma the autoactivation of factor XII and the activation of prekallikrein, resulting in an increase of the effective concentration of kallikrein and possibly other proteases and proteolysis of LDL-apoB-100. The higher degree of the DS-induced proteolysis of apoB-100 at 0 degrees C than at 23 degrees C is likely the consequence of enhanced autoactivation of factor XII and a decreased efficiency of plasma inhibitors, such as C1-inhibitor. We speculate that the proteolysis of apoB-100 induced by DS is not limited to this polyanion, but may also be the property of other negatively charged agents, particularly at cold temperatures.

Apolipoprotein B-100↗

[Beta-enolase in blood plasma during open heart surgery--comparing with CK-MB and CA-III in blood plasma].

Enolase isozyme composed of the beta subunit (alpha beta or beta beta enolase) is distributed predominantly in the heart and skeletal muscles. Concentrations of beta-enolase (beta subunit of enolase) in blood plasma samples serially taken from 18 patients, who received mitral valve replacement, were estimated by using a highly sensitive enzyme immunoassay method and compared with those of CK-MB in the same samples. Plasma beta-enolase levels, that were 6.60 +/- 3.84 ng/ml at the beginning of anesthesia, increased rapidly after reperfusion reaching the plateau more than 100 ng/ml between 2 to 12 hours, showing two peak (116 +/- 45.7 ng/ml at 4 hours and 112 +/- 48.1 ng/ml at 12 hours after reperfusion), and then decreased slowly remaining high levels even when plasma CK-MB levels became normal. The beta-enolase concentrations were significantly higher in coronary sinus samples than in arterial samples early after reperfusion. Since plasma carbonic anhydrase III, which is known to be localized only in the skeletal muscle, did not increase during the surgery, it is suggested that the major portion of elevated plasma beta-enolase levels were derived from the heart muscle. Plasma levels of beta-enolase increased as quickly as those of CK-MB after reperfusion and kept high levels longer than those of CK-MB. These results indicate that the determination of beta-enolase in plasma may be useful for estimating the myocardial damage during open heart surgery.

Carbonic Anhydrases↗

[Influence of tooth extraction on the CT level in plasma. Influence on the plasma Ca-P levels during the postextraction healing after CT administration].

The constant concentration of calcium ions (Ca2+) in the extracellular fluids can be maintained by two mechanisms; the local and the hormonal one. In the case of the local, a potential Ca2+ balance is achieved between the extracellular space on the one hand and the bones and intertine on the other hand, which may come to concentrations of 7 mg/100 ml. The complete settlement of the Ca2+ level up to the normal limits of 9-11 mg/100 ml of plasma, is achieved by the action of the hormonal mechanism. This acts through a negative ruccessive muctual control. The hormonal mechanism includes the action of basically two hormones, the parathormone (PTH) and the calcitonine (CT). The first one is secreted when the Ca2+ level in plasma decreases, causing the increase of the renal tubular reabsorption of Ca2+, the release of Ca2+, due to the increased absorption in bones and the increased intestinal Ca2+ absorption. By that way the Ca2+ normal level in plasma is resettled. On the other hand, in case of an increase of the Ca2+ level in plasma, the excretion of PTH is restrained whereas CT is secreted, which favours the deposition of Ca2+ on bones restricting their absorption at the same time. In several cases, when there is an organic inability of resettling any change of the Ca2+ balance due to the malfunction of the hormonal mechanism, various drugs are being given for treating the disease. The balance, being achieved this way, may be overtured by several factors such as bone fractures as it has been observed experimentally, and may cause the increase of the Ca2+ concentration in plasma. In the present experimental study, the possibility of a proportional increase in the secretion of the CT after a simple and surgical extraction has been investigated. The possibility of an alteration of the Calcium and Posphate levels in plasma after the supply of CT during certain intervals has also been investigated. The results showed that the extraction does not change the CT levels in plasma. On the other hand the Ca2+ and P levels, are not affected by the external supply of CT, for reasons which are being discussed in the present paper.

Calcitonin↗

Effects of san-huang-hsieh-hsin-tang on sympathetic activity, plasma renin, and plasma aldosterone.

San-Huang-Hsieh-Hsin-Tang, an ancient Chinese remedy for gastrointestinal disorders, was also found to lower blood pressure. The authors therefore investigated the effects of this substance on sympathetic activity, plasma renin, and plasma aldosterone. Sympathetic activity and plasma renin activity, but not plasma aldosterone levels, were significantly reduced with treatment. The depressed plasma renin activity could be secondary to depressed sympathetic activity. The discrepancy between plasma renin activity and plasma aldosterone levels, which is also found with beta-blockers, could be explained by the following sequence: decreased renin----decreased aldosterone----increased serum potassium----recovery of aldosterone.

Aldosterone↗

Response of plasma vasopressin to changes in extracellular volume and/or plasma osmolality in patients on maintenance hemodialysis.

The effect of changes in extracellular volume versus changes in plasma osmolality on arginine vasopressin (AVP) release was studied in 6 patients with terminal renal failure maintained on chronic hemodialysis. The day of the study, the patients were treated by sequential ultrafiltration lasting 1 hour followed by a 3-hour conventional hemodialysis session. The ultrafiltration resulted in the removal of 460 to 1,170 ml (mean = 860 ml) of volume. Body weight during the combined procedures fell by 1.6 +/- 0.4 kg (mean +/- s.e.m.) while mean arterial pressure decreased only slightly. Plasma osmolality was unaffected by sequential ultrafiltration, but decreased from 313 +/- 4 mosm/kg H2O to 291 +/- 4 mosm/kg H2O during hemodialysis. Initial plasma AVP concentration was high at 4.45 +/- 0.25 pg/ml and remained unchanged during the sequential ultrafiltration at 4.55 +/- 0.37 pg/ml, but it fell during the hemodialysis to 2.47 +/- 0.45 pg/ml. A hypotensive episode observed in one patient towards the end of hemodialysis resulted in a sharp increase in plasma AVP concentration from 5.5 to 18 pg/ml. During the combined procedures, plasma AVP and plasma osmolality showed a close and linear correlation (r = 0.63, n = 23, p less than 0.001). These findings suggest that in patients on maintenance hemodialysis, changes in plasma osmolality play a predominant role in determining AVP secretion whereas a marked decrease in volume without ensuing hypotension has no effect on AVP release.

Blood Pressure↗

A proenzyme from chicken plasma similar to human plasma prekallikrein.

We report the isolation of a specific protease zymogen from chicken plasma. The purification procedure involves barium citrate precipitation, ammonium sulfate fractionation, removal of plasminogen and plasmin on lysine-Sepharose, followed by anion and cation exchange, and gel permeation chromatography. Based on quantitative radioimmunoassay the zymogen is present in plasma at a concentration of 160 mg/liter, and it is obtained by our procedure in highly purified form with a yield of 1.4%. The single polypeptide chain contains an NH2-terminal alanine residue. The native molecule migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 84,000 under reducing conditions. It can be identified as an inactive proenzyme because it has very low amidolytic activity, does not react with the fluorescent active site titrant 4-methyl-lumbelliferyl p-guanidinobenzoate, and does not incorporate radioactive [3H]diisopropylfluorophosphate. It is very susceptible to limited proteolysis which converts it to an active enzyme with trypsin-like specificity. The active enzyme, likewise a single polypeptide chain, migrates as a doublet with apparent molecular weights of 39,000 and 40,000. Its amidolytic activity with synthetic peptide substrates is at least 40-fold higher than that of the proenzyme, it reacts efficiently with 4-methylumbelliferyl p-guanidinobenzoate, and incorporates [3H]diisopropylfluorophosphate while undergoing irreversible inactivation. The enzyme appears to be a reasonably efficient plasminogen activator in zymographic gels, but not in solution. With human high molecular weight kininogen as substrate the enzyme was about 25% as efficient as human plasma kallikrein. It lacks any plasminogen-independent proteolytic activity with other protein substrates, and it hydrolyzes small peptide substrates designed for both human kallikrein and urinary urokinase, respectively. Inhibition studies with peptide chloromethyl ketones indicate enzymatic properties closer to human plasma kallikrein than to the human plasminogen activator urokinase (EC 3.4.21.31). The chicken plasma enzyme and the plasminogen activator from the conditioned media of Rous sarcoma virus-transformed chick embryo fibroblasts treated with tumor promoter are different by criteria of tryptic peptide maps, and amino acid composition and enzymatic specificity. The designations chicken plasma prekallikrein plasminogen proactivator and chicken plasma kallikrein plasminogen activator are proposed for the zymogen and enzyme forms, respectively. Using rabbit antibodies against the proenzyme we developed a solid phase immunoadsorption procedure that allowed us to isolate the protein with an overall yield of 11.4%.

Amino Acids↗

Relationship between plasma volume reduction and plasma electrolyte changes after prolonged bicycle exercise, passive heating and diuretic dehydration.

Plasma volume was decreased by prolonged bicycle exercise, by passive heating in warm water, by sauna dehydration, and by diuretically induced dehydration in eleven well trained subjects. Blood samples from an arm vein were taken before and after this pre-treatment, as well as after a subsequent standard exercise test (SET) on a bicycle ergometer (50%, 70% and 105% of max VO2; the SET with no pre-treatment was used as a control condition. The changes in plasma concentration of Na+, K+ and Cl- were not proportional to the calculated plasma volume changes. The Na+ and Cl- concentrations always increased in the plasma, while plasma potassium concentration was increased after prolonged exercise, but decreased after the other types of dehydrations. The standard exercise test produced a pronounced fall in total calculated plasma potassium and in K+ concentration measured 3-5 min after exercise in all types of experiments. In the standard exercise test the calculated water loss from the plasma volume was relatively large. It amounted to about 2/3 of the total water loss in the standard exercise test and was independent of the pre-treatments.

Blood Volume↗

Distribution of plasma fibronectin (cold-insoluble globulin) and components of the factor VIII complex after heparin-induced precipitation of plasma.

Factor VIII procoagulant (VIII:C) activity, factor VIII coagulant antigen (VIII:CAg), von Willebrand ristocetin cofactor (VIIIR:RC) activity, factor VIII-related antigen (VIIIR:Ag), and plasma fibronectin (CIg; cold-insoluble globulin) were measured in the heparin precipitable fraction (HPF) and heparin supernatant fraction (HS) of normal human plasma. Following heparin induced precipitation, most measurable VIII:C activity (77% +/- 24%) was recovered in the HS. Although there was little VIII:C activity (less than 1%) in the HPF, 20% +/- 6.5% VIII:CAg was present as well as CIg (81% +/- 5.6%). VIIIR:RC activity (72% +/- 12%), and VIIIR:Ag (34 +/- 5.2%). As assessed by Na dodecyl SO4 glyoxyl agarose electrophoresis, the multimeric forms of plasma VIIIR:Ag could be resolved into a series of bands. Larger multimers tended to precipitate with the HPF whereas the smaller multimers tended to remain supernatant. Plasma from a subject with congenital afibrinogenemia was also studied. Although the afibrinogenemic HPF contained CIg, neither VIIIR:RC activity nor VIIIR:Ag was precipitated. However, both were present in the HPF from afibrinogenemic plasma to which fibrinogen had been added, suggesting that they are incorporated in this precipitate because of an affinity for fibrinogen. The ability of heparin to induce precipitation of CIg while leaving most VIII:C activity in the supernatant plasma may be useful in the preparation of procoagulant-rich plasma subfractions, since VIII:C can subsequently be recovered in good yield by cryoprecipitation.

Afibrinogenemia↗

Reversible and irreversible interactions of a cisplatin analog bearing a 1,2-diphenylethylenediamine ligand with plasma and plasma proteins in vitro.

The cisplatin analog [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl) ethylenediamine]dichloroplatinum(II) [PtCl2(1)], by virtue of its estrogenic 1,2-diphenylethylenediamine ligand 1, was intended to function as a cytotoxic estrogen. This article reports on the reversible and irreversible interactions of this compound with plasma and plasma proteins in vitro. At 37 degrees C [PtCl2(1)] is > 99% reversibly bound to proteins in plasma. At 0 degree C [PtCl2(1)] reversibly binds to albumin at specific binding sites not shared by 1. By use of HPLC the in vitro half-life of total [PtCl2(1)] in plasma was found to be 35 min at 37 degrees C, which is approximately 1/3 the half-life reported for cisplatin under similar conditions. To understand this decreased stability, irreversible reactions of [PtCl2(1)] with albumin and plasma globulins were investigated. The reaction rate of [PtCl2(1)] with albumin is independent of the protein concentration and is comparable to the rate of the first Pt-Cl hydrolysis reaction. Thus, [PtCl2(1)], like cisplatin, reacts irreversibly with albumin through a solvent-assisted SN2 substitution pathway. Because the hydrolysis rate for [PtCl2(1)] is 40% slower than for cisplatin, irreversible reactions of [PtCl2(1)] with albumin cannot account for the decreased stability of the compound in plasma. alpha-Globulins undergo substitution reactions with [PtCl2(1)] by both solvent-assisted and direct SN2 pathways. The half-life of [PtCl2(1)] in the presence of alpha-globulins at concentrations normally present in plasma (6-16 g/liter) is from 41 to 22 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-Globulins↗

Growth hormone concentrations in mammary secretions and plasma of the periparturient bitch and in plasma of the neonate.

The presence of growth hormone (GH) in mammary secretions of bitches was investigated in relation to plasma GH concentrations at about the time of parturition and during the first weeks of lactation. Plasma GH concentrations in neonates were measured during the first weeks of lactation, to determine whether GH in maternal milk contributes to plasma concentrations of GH in the neonate. Gastrointestinal uptake of GH was studied by measurement of plasma bovine GH (bGH) concentrations after intragastric administration of bGH. High concentrations of GH were found in the mammary secretions of the bitches, particularly before parturition and in colostrum, exceeding maternal plasma concentration up to 100-1000 times. GH concentrations in milk were not not significantly correlated with GH concentrations in plasma of bitches or neonates. Bovine GH could not be detected in neonatal plasma for 4 h after intragastric administration of bGH. The presence of high concentrations of canine GH (cGH) in ante-partum and colostral mammary secretions is consistent with the progesterone-induced mammary biosynthesis of GH. GH in milk is probably not absorbed from the gastrointestinal tract into the blood circulation of the newborn in its intact form.

Animals↗

Incidence of allergic reactions with fresh frozen plasma or cryo-supernatant plasma in the treatment of thrombotic thrombocytopenic purpura.

Plasma replacement for thrombotic thrombocytopenic purpura (TTP) is accomplished with various plasma products. This study sought to determine the incidence of allergic reactions with FFP or CPP as replacement in therapeutic plasma exchange (TPE). Forty-one TTP patients were identified retrospectively who received TPE replacement with either FFP (n=21) or CPP (n=20). Anti-histamine was administered prophylactically following the initial occurrence of an allergic reaction (urticaria, respiratory distress, or anaphylaxis with hypotension). Fifty-one allergic reactions occurred in 65.8% of patients. Urticaria comprised 49 of 51 (96%) of reactions and respiratory distress the remaining 4%. No anaphylaxis occurred. Nineteen urticarial reactions occurred in 50% of CPP recipients compared to 71% of FFP recipients (P=0.28). Anti-histamine breakthrough occurred in 36.3% of patients who experienced a previous allergic reaction with CPP and 37.5% with FFP (P=1.0). The overall risk of allergy per unit of plasma was 1.37% (1.23 % CPP, 1.48% FFP), comparable to estimates in non-TTP recipients. The median number of donor exposures preceding the first allergic reaction was 35 and 32, CPP and FFP, respectively (P=0.63). The mean volume of plasma transfused prior to reaction was 9,883 mL for CPP and 9,348 mL for FFP (P=0.85). Neither product was advantageous in preventing allergic complications. Because of the large volume, the number of donor exposures, and prolonged duration of therapy, allergic reactions to plasma are common (65.8%) in the treatment of TTP.

Blood Preservation↗

IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung.

The association between IgG4 dysregulation and inflammatory pseudotumor (IPT) was first reported in sclerosing pancreatitis. Recently, we described IPTs of the liver and breast, into both of which many IgG4-positive plasma cells had infiltrated. In this study, we examined the clinical and histological features of 9 cases of IPT (histologically corresponding to plasma cell granuloma) of the lung with an emphasis on IgG4-positive plasma cell infiltration. The lesions were characterized histologically by dense lymphoplasmacytic infiltrates intermixed with fibrosis and, in some cases, prominent eosinophilic infiltration, irregular narrowing of bronchioles entrapped in nodules, and an interstitial pneumonia pattern at the boundaries of nodules. Obliterative phlebitis was easily found in all cases, and 5 lesions also had obliterative arteritis. Immunostaining revealed many IgG4-positive plasma cells diffusely distributed within nodules, and the ratios of IgG4-positive to other plasma cells were extraordinarily high. Of the 9 patients, 8 underwent surgical treatment and in 1 patient, lesion was diagnosed on transbronchial biopsy and effectively treated with corticosteroid. Two cases were associated with chronic sclerosing sialadenitis or lymphadenopathy, in which many IgG4-positive plasma cells were also identified by immunostaining. The clinicopathologic similarities between IPT of the lung and sclerosing pancreatitis suggest that IgG4-related immunopathologic processes might be involved in the pathogenesis of the pulmonary lesions.

Adult↗

Therapeutic plasma exchange and plasma infusion in thrombotic microvascular syndromes.

Plasma exchange (PE) is the most important treatment in thrombotic microangiopathies (TMAs) mainly encompassing thrombotic thrombocytopenic purpura (TTP) and adult hemolytic syndrome (HUS). This therapeutic measure has substantially improved clinical outcome. One plasma volume corresponding to 40 ml/kg of body weight is exchanged daily until the platelet count is above 150 x 10(9)/l or 100 x 10(9)/l and continues to rise or remains constantly after cessation of treatment. Exacerbations and late recurrences demand reapplication of daily PE. Twice daily PEs are initiated if the response to initial treatment is poor. The importance of additional or alternate measures including glucocorticoids, antiplatelet agents, splenectomy, intravenous immunoglobulins, protein A columns, vincristine, cyclosporine, and cyclophosphamide is uncertain. Whether cryosupernatant plasma (CSP) or solvent/detergent-treated (SDP) plasma is superior to standard fresh frozen plasma (FFP) remains to be determined. Methylene blue-treated plasma (MBP) seems to be less effective than standard FFP.

Hemolytic-Uremic Syndrome↗

Fresh-frozen plasma vs. plasma protein derivative as adjunctive therapy for patients with massive burns.

Twenty patients with burn injuries involving 45% or more total body surface area were randomly allocated to receive either fresh-frozen plasma (plasma), 200 ml/m2/d (11 patients), or an approximately equal amount of plasma protein derivative (Plasmanate) (nine patients) during the first 45 days postburn. To study the potential effects of these two adjunctive therapies on host resistance to infection, measurements were made twice weekly of the antibacterial funciton of neutrophils, the opsonic index (ability to opsonize alternative pathway dependent E. coli 075), C3(B), IgG, properdin, factor B, total protein, and albumin. The average size of burn in the plasma group was 61.5% total and 42% 3 degrees compared with 61% total and 46% 3 degrees in the Plasmanate group. Ten and 18 episodes of bacteremia occurred in the plasma and Plasmanate groups, respectively. Analysis of the results indicates only slightly better support of host resistance when plasma is administered, but this is counterbalanced by the increased risk of viral hepatitis.

Adolescent↗

Tumor necrosis factor and interleukin 1 appearance in experimental gram-negative septic shock. The effects of plasma exchange with albumin and plasma infusion.

To study the effect of plasma removal vs plasma administration on the appearance of tumor necrosis factor (TNF) and interleukin 1 in septic shock, 24 anesthetized piglets were inoculated with live Escherichia coli. Plasma exchange with albumin was performed in one group. Fresh-frozen plasma was administered to a second group. A third group served as nontreated controls. Following plasma exchange, a reduction in both TNF and interleukin 1 levels occurred, whereas plasma infusion was followed by a decrease in TNF levels only. No significant differences were observed between the two treated groups with respect to survival or cardiovascular performance, with both being significantly enhanced compared with the controls. High levels of TNF and interleukin 1 correlated with depressed cardiovascular performance in the early phase of the shock. Our results confirm the important role of TNF and interleukin 1 as early mediators of septic shock. However, the benefit of reducing cytokine activity in later stages of septicemia seems to be dubious.

Animals↗

Plasma catecholamine assays: calibration with spiked plasma versus aqueous solutions.

Both aqueous standards and plasmas spiked with standards are used for assays of plasma constituents. In a previous study, high-performance liquid chromatographic (HPLC) assays of plasma norepinephrine, epinephrine, and dopamine performed with spiked plasma reference solutions resulted in lower thresholds and thus gave higher concentrations. To verify the hypothesis that spiked catecholamines bind to plasma proteins (like physiological catecholamines) and thus escape extraction by alumina prior to HPLC, the recovery of standards in human albumin solution was compared with similar investigations using aqueous standards. Our findings confirm that (a) albumin is responsible to a great extent for the drop in recovery and (b) calibration by extraction of aqueous standards is preferable to calibration by spiked plasma for free catecholamine assays.

Blood Proteins↗

Partial plasma protein replacement in therapeutic plasma exchange.

We wished to determine whether subtotal replacement of protein in plasma removed at plasma exchange would be adequate to prevent hypovolemia and hypoproteinemia. Seven well nourished outpatients with chronic progressive multiple sclerosis underwent 60 plasma exchanges in which two liters of plasma were replaced with 750 ml saline followed by 1250 ml of a 5% albumin solution (62.5% albumin replacement). Total serum protein, protein electrophoresis, and immunoglobulin levels were measured before and after each exchange. Clinically, the exchanges were well tolerated. Total serum protein dropped by a mean of only 18% during the study and mean preexchange serum albumin levels were unchanged, even though immunoglobulins decreased by 57-72%. We conclude that in well nourished patients, partial albumin replacement of this magnitude is an adequate substitute for plasma removed in a plasma exchange.

Adult↗