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Can plasma fructosamine substitute for glycated haemoglobin (HbA1c) estimation in the assessment of diabetic control?

The 'gold standard' marker of overall glycaemic control in diabetes mellitus is the level of glycated haemoglobin (HbA1c). It is, however, an expensive and technically difficult assay and is rarely appropriate to tropical laboratories. Plasma fructosamine measurement is cheaper and easier, though it reflects shorter-term glycaemia. We have measured both indices of control in a group of 154 diabetic patients. There was close correlation between the two measurements (r = 0.6506, P < 0.001), but many patients with abnormal HbA1c levels had normal fructosamine levels. This resulted in an assay sensitivity (compared with HbA1c as gold standard) of only 30%, though specificity was 98%. We conclude that fructosamine measurement cannot be regarded as a substitute for HbA1c determination.

Adolescent↗

IgE-mediated allergic reactions to fruit gums and investigation of cross-reactivity between gelatine and modified gelatine-containing products.

A 32-year-old female reacted with a contact urticaria syndrome after eating 'gummy bears' (fruit gums). The reaction began in the oral mucosa and led to treatment on an inpatient basis. RAST measurements with allergen discs produced with gelatine and gelatine-containing products (among them 'gummy bears') demonstrated the presence of IgE antibodies in the serum of this patient. Proteins with molecular weights in the range of 40-120 kD were identified as the allergens in gelatine by using Western blot analysis. RAST inhibition showed cross-reactivity between gelatine, gelatine-containing products and the modified gelatine used in some plasma substitutes. Allergic reactions towards coloured fruit candies and 'gummy bears' may result from an IgE-mediated hypersensitivity towards gelatine. The long-known anaphylactoid reactions towards gelatine-containing plasma substitutes may, at least in part, be of an allergic nature.

Adult↗

[Erythrocyte, plasma and substitute hemoglobins facing physiological oxidizing and reducing agents].

Oxidation of hemoglobin is constant and normal in red blood cells and in all biological media. The knowledge of the mechanisms which manage oxidation state is perhaps sufficient to treat acquired and some hereditary methemoglobinemia. But in case of transfusional treatment with hemoglobin based oxygen carrier (HBOC), some preclinical investigations on the oxidation of these products in vivo in plasma showed that our knowledge was not sufficient to understand and control all oxidations which could occur. This review analyses the literature on the different mechanisms in red blood cells and plasma by which hemoglobin autooxidizes and by which endogenous oxidizing agents or their precursors (nitric oxide, peroxynitrite, superoxide, hydrogen peroxide) could oxidize it. It shows the production of different radical or non-radical oxygen species during hemoglobin autooxidation and oxidation processes and the different physiological or accessory mechanisms that could prevent or reduce the various oxidizing states of hemoglobin (HbFe3+, HbFe4+) in blood. Plasma contains a few anti-oxidizing or reducing systems but it profits by antioxidizing and reducing activity from red blood cells. In blood, oxidation state of hemoglobin results from very complex phenomena and if the body struggles against methemoglobin formation to maintain oxygen transport, the oxidation of hemoglobin is sometimes useful to protect tissues against various and numerous endogenous radical or non-radical oxidizing agents. In blood, a balance between all these oxidizing and reducing mechanisms makes it possible to regulate circulating methemoglobin rate.

Antioxidants↗

[Hemodilution in patients with stage IIb peripheral arterial occlusive disease: prospective randomized double-blind comparison of middle-molecular weight hydroxyethyl starch and low-molecular weight dextran solution].

Isovolemic hemodilution is a simple method of treating patients with peripheral arterial occlusion disease and hematocrit values of 43% or more. Dextran, a plasma substitute, has been used for that purpose since the early 1950s. However, the use of dextran in some diseases, e.g., hemorrhagic diathesis, kidney insufficiency, and microangiopathy is not without risk. Anaphylactic reaction, too, has occurred in some cases. Since the end of the 1970s hydroxyethyl starch, a plasma substitute, is available for the therapy of microcirculatory disorders and hemorrhagic diathesis. The side effects of hydroxyethyl starch are less serious and anaphylactic reactions are less frequent and moderate in extent. The clinical efficacy of both substances was compared in this survey. It could be stated that middle molecular hydroxyethyl starch is even clinically superior to low molecular dextran because the distance that the patients could walk increased significantly.

Arterial Occlusive Diseases↗

Nine years of cascade filtration for thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) continues to attract physicians' attention because of its unpredictable course and underlying pathogenetic mechanisms. It is also attractive because of its optimal response to therapeutic plasma exchange (PE) even in the most severe cases. The usual approach to its treatment is conventional PE with plasma substitution and only recently fresh frozen plasma (FFP) has been substituted by cryodepleted or virally inactivated plasma with clinical results that are, if not better, at least comparable with the ones attained when FFP is employed. Nonetheless, no consensus exists regarding the optimal PE fluid and this is not of marginal interest as even after PE treatment mortality is still from 15 to 20%. On the contrary, some consensus exists on the pathogenetic relevance of the exceedingly large Von Willebrand (vWF) multimers whose presence parallels the clinical course and appears to be determined by the abnormalities in the production or function and survival of vWF-cleaving proteases which is auto-antibody mediated. In both cases plasmapheresis without plasma infusion is relatively ineffective, perhaps because it does not increase protease activity. Paradoxically, cascade filtration (CF) can produce the same favorable results without replacing any protease activity. As with CF, the replacement is the autologous plasma with approximately 20% levels of vWF, fibrinogen, fibronectin, IgM and circulating immune complexes and 75% of albumin, IgGs, AT III and proteins whose molecular weight exceeds 250-300000 Da. Our experience with CF for TTP began in 1994. Since then, 16 patients have undergone CF combined with decreasing amounts of FFP supplementation and since 1998 without any allogeneic FFP supplementation in 9 cases. Twenty-four patients (96%) treated with no or minimal amounts of FFP survived but four (16%) experienced from one to four recurrences associated with cutaneous, paradental, cholecystic and vaginal infections. Only one patient died (5%) after the second CF procedure. There were no untoward effects related to the procedure itself and up to 18 procedures in one patient were carried out over 16 months, 10 with the patient in her sixth month of pregnancy and four in the post partum period in preparation for a splenectomy. Remission was achieved after an average number of treatments (10.7 +/- 6.8); a result that compares favorably with those of our historical control group of 47 cases (14 +/- 13). The patient's exposure to allogenic plasma which was 10.8 +/- 4.6 plasma U/session was reduced to 0 in 10 patients, to 1.4 +/- 1.2 and 4.4 +/- 2.3 plasma U/session, respectively, for seven and nine patients receiving PE + CF and CF with same plasma supplementation as described in our previous article. Based on our experience, we believe CF is presently the optimal treatment for patients with classic, sporadic TTP.

Female↗

Decrease of angiotensin-converting enzyme activity after plasma exchange.

We measured sequential changes in serum angiotensin-converting enzyme (ACE) in 12 ICU patients undergoing plasma exchange (PE) with plasma substitutes (albumin-Polygelin). A dramatic decrease in serum ACE activity was observed after each of the 51 PE procedures. Repeated PE procedures resulted in almost a total depletion of serum ACE, which returned to normal ranges in 4 to 10 days. No ACE change was observed during hemodialysis or hemofiltration. ACE activity increased after PE with fresh frozen plasma replacement. ACE changes were compared with IgG, antithrombin III, and fibronectin changes. Extraction ratio comparisons were consistent, with a loss in removed plasma accounting for 50% to 70% of the observed ACE decrease. Plasma zinc levels were not modified after PE. Mixing experiments with increasing volumes of plasma substitutes showed ACE inhibition by Polygelin. In vivo infusion of Polygelin had the same effect. The renin-induced aldosterone response studied in six exchanged patients was consistent with a relative hyperreninemic hypoaldosteronism after repeated PE. These findings may be of clinical relevance during acute hypovolemia and dehydration after PE or Polygelin infusion and in patients with impaired lung endothelial function.

Adult↗

[Discontinuous plasma exchange with the conventional hemodialysis technic and blood cell centrifugation].

A conventional haemodialysis system, to which the patient is connected as for acute dialysis, forms the basis of the plasma substitution method. At each session around 2 litres of plasma were exchanges within 3 hours. Freshly frozen donor plasma was mainly used as the substitution solution. A total of 20 substitutions were carried out in 5 patients in a period of 7 months. The indications were: 3 x major mismatch in the ABO system before bone marrow transplantation, myasthenic crisis, violent attacks connected with lupus erythematosus with rapid development of renal insufficiency. The therapeutic goal of quickly eliminating immunopathogenetic proteins was achieved in all cases. It was possible to reduce the level of isoagglutinins, haemolysins, autoantibodies (myasthenia gravis) and immunity complexes (LE) effectively. The clinical course confirmed the excellent effectivity. There were no serious complications despite the serious primary diseases. Volume imbalances, changes of body temperature, precipitations of cryoglobulins, electrolyte disturbances or citrate intoxications were always well controllable thanks to the combination of plasma substitution and dialysis.

ABO Blood-Group System↗

Significance of fluid flow for morphology of acute hypoxic-ischaemic brain cell injury.

It has been suggested that the presence or absence of hypoxic fluid flow during ischaemia determines the structural character of the ischaemic nerve cell injury. It is hypothesised that if a flow of fluid irrigates the injured neurons, there will be major shifts of ions and water, with consequent volumetric changes in the tissue and the 'dark' type of neuronal injury will result; otherwise, the structural changes are less striking and are designated as the 'pale' type. To test this hypothesis, rats were subjected to a global cerebral insult by filling the vasculature with a plasma substitute, which was either left stagnant or was flowing, and was either oxygenated (hypoxic flow) or nitrogenated (anoxic flow). Light and electron microscopy of the brain following 10 to 60 min of hypoxic or anoxic ischaemia disclosed that, under all three circumstances, the predominant nerve cell injury was of the pale type. The results indicate that some additional factors present in whole blood (but not in the plasma substitute) are needed during or after the insult to induce in quantity the dark type of ischaemic nerve cell injury.

Acute Disease↗

Fluorocarbons. Current status and future applications.

This article presents information on medical applications of fluorocarbons. These inert chemicals have a high solubility for the respiratory gases and, in emulsified form, are present in the oxygen-transporting plasma substitutes now undergoing clinical trials. Oxygen content is directly related to arterial partial pressure of oxygen (PaO2). Thus, although oxygen transport of Fluosol-DA 20% (FDA) is only 0.75 ml per 100 ml per 10 kPa, oxygen delivery at the tissues will be adequate in the presence of a high PaO2. FDA has a low viscosity at low shear rates and this, together with a very small emulsion particle size of 0.1 micron, helps provide improved tissue oxygenation in conditions of ischaemic hypoxia. Fluorocarbon plasma substitutes may be employed as 'blood', but may also be used for a wide range of purposes in clinical practice. This review describes some current and potential future applications.

Biological Transport↗

Acute plasma volume expansion: effect on metabolism during submaximal exercise.

To examine the effect of acute plasma volume expansion (PVE) on substrate selection during exercise, seven untrained men cycled for 40 min at 72 +/- 2% peak oxygen uptake (VO(2 peak)) on two occasions. On one occasion, subjects had their plasma volume expanded by 12 +/- 2% via an intravenous infusion of the plasma substitute Haemaccel, whereas on the other occasion no such infusion took place. Muscle samples were obtained before and immediately after exercise. In addition, heart rate and pulmonary gas and venous blood samples were obtained throughout exercise. No differences in oxygen uptake or heart rate during exercise were observed between trials, whereas respiratory exchange ratio, blood glucose, and lactate were unaffected by PVE. Muscle glycogen and lactate concentrations were not different either before or after exercise. In addition, there was no difference in total carbohydrate oxidation between trials (control: 108 +/- 2 g; PVE group: 105 +/- 2 g). Plasma catecholamine levels were not affected by PVE. These data indicate that substrate metabolism during submaximal exercise in untrained men is unaltered by acute hypervolemia.

Adult↗

A model of closed chest regional myocardial infarction in the rabbit: a clinically relevant in vivo assay system of post-infarction remodelling.

Coronary artery ligation is the standard technique to induce regional myocardial infarction in small animal models. However, opening the chest and incising the pericardium independently influence post-MI remodelling. Our purpose was to develop and characterize a novel closed chest model of regional myocardial infarction (MI) in the rabbit of increased clinical relevance. Coronary angiography was performed percutaneously in New Zealand White Rabbits (NZW) using pre-formed catheters. A 0.36 mm thrombogenic coil was positioned in the circumflex artery to induce closed chest MI. Of rabbits undergoing coil deployment 40 % survived until day 100. Rabbits were classified as small MI (n = 5), moderate MI (n = 6) and large MI (n = 6) < 15 %, 15 - 30 %, > 30 % of LV myocardial volume respectively) or sham controls (n=11). Transthoracic echocardiographic images were obtained 0, 3, 5, 7, 14, 28, 60, 100 days post procedure. At day 100, LVEDP was measured before and after plasma substitute infusion. Hearts were subsequently excised and chamber stiffness (Kc) was derived from the passive pressure-volume relationship. Cardiac weight, dimensions and MI as a percentage of LV volume (MI%) were also recorded. Differences in percentage fractional shortening (%FS) were apparent from day 14. %FS was reduced in rabbits with large and moderate MI compared to controls (day 100, p < 0.005 and p < 0.05, respectively). LVEDP was increased in large and moderate MI compared to small MI and controls (26 mmHg +/- 6 and 21 mmHg +/- 5 vs. 9 mmHg +/- 1 and 7 mmHg +/- 3 p < 0.005); these differences were maintained during plasma substitute infusion. Kc in large MI was significantly less than moderate MI, small MI or control (all p < 0.05). Direct morphometric measurements distinguished between all groups.This study provides the first description of post-infarction remodelling after coronary artery occlusion where the pericardium remains intact in a small animal model. We believe it may provide a more physiologically and clinically relevant in vivo assay system of left ventricular dysfunction after myocardial infarction.

Animals↗

[Blood physiological resources and their role in physiological adaptation of the body to blood loss (based on the experimental data and calculations)].

In white rats, loss of about 66 +/- 3% of the blood volume results in an abrupt drop of the BP and arrest of the lung respiration. Introduction of a plasma substitute in the volume equal to the lost blood resulted in an increase of the BP and restoration of rhythmical respiration in 9 out of 14 experimental rats. Haematocrit after the blood loss and subsequent administration of the substitute was about 15%. Previously obtained data show that the Ht of about 15% decreases the oxygen transport to tissues. However, an increase in the lung ventilation, a shift of the haemoglobin dissociation curve to the right, an increase of oxygen extraction from the blood, and an increase in the minute blood volume by 50-100%, allow a sufficient oxygen transport to the organism tissues to be ensured at the Ht of about 15%. Thus, the reserve of the blood respiration function of the blood remaining after a life-threatening blood loss plays an important physiological role in replenishing the volume of the lost blood with the plasma substitute and in survival of the organism.

Animals↗

Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients with acute coronary syndromes and in healthy subjects : impact of the V264M substitution on plasma levels of TFPI.

-Mutations of the gene encoding tissue factor pathway inhibitor (TFPI), an inhibitor of TF-induced activation of the coagulation cascade, were screened for in 130 patients and 142 healthy controls to determine whether these variants contribute to acute coronary syndromes or modify plasma TFPI levels. The following 3 new polymorphisms were identified: 384T-->C in exon IV, which does not change the corresponding amino acid (tyrosine 57); -33C-->T in intron 7 (the T/T, C/T, and C/C genotypes were found in approximately 50%, 40%, and 10% of subjects in both groups); and 874G-->A in exon IX (GTG-->ATG), which predicts a valine to methionine change (V264M) in the carboxy-terminus tail of TFPI. The V264M polymorphism was found in 9.2% of the cases and 4.9% of the controls; the associated odds ratio (OR) for acute coronary syndromes was 2.0 (95% confidence interval [CI], 0.7 to 5.1). The OR increased to 3.6 (95% CI, 0.8 to 15.7) and 3.2 (95% CI, 0.9 to 11.8) in nonsmokers and patients without other risk factors, respectively. The possible link between the V264M polymorphism and coronary heart disease was checked in a large case-control study of myocardial infarction (Etude Cas-Témoins de l'Infarctus du Myocarde [the ECTIM Study]). The results showed no link between the V264M polymorphism and coronary syndromes. Interestingly, however, 5 patients heterozygous for the V264M polymorphism had significantly lower plasma TFPI levels than did 13 patients with the most common genotype. Although our present results do not support an association between TFPI polymorphisms and acute coronary syndromes, the possibility that 1 of them, especially the exon IX polymorphism, is associated with subtypes of myocardial infarction or to evolutive particularities that were not assessed in this study, cannot be excluded and is currently being evaluated.

Acute Disease↗

[Modified hemoglobin solutions as artificial oxygen carriers].

At least theoretically, hemoglobin (Hb) solutions are ideal colloidal plasma substitutes because of their unique ability to take up oxygen, transport it in bound form, and release it peripherally. The present study gives an overview of the development and present status of modified Hb preparations. While human and bovine erythrocytes are used for production on the one hand, human Hb variants can also be derived from yeast or bacteria as well as via transgenic animals through recombinant DNA technology. The pronounced limitations of extraerythrocytic Hb, that is its high oxygen affinity and its inadequate intravascular persistence, can be overcome by various modifications. Intravascular half-life of free Hb can be significantly increased by intramolecular stabilization, linking to macromolecules, intermolecular cross-linking (PolyHb solutions) or microencapsulation. Oxygen affinity of human Hb may be lowered by coupling of allosteric modulators to the 2,3-bisphosphoglycerate site, e.g. pyridoxal phosphate, whereas bovine Hb has an intrinsically low oxygen affinity. Human pyridoxylated PolyHb solutions and bovine PolyHb solutions presently fulfill at least 2 of the 3 principal requirements for an oxygen-transporting plasma substitute, i.e. maintenance of the circulating blood volume with provision of additionally utilizable oxygen capacity. Matters of concern with all Hb preparations remain potential vasoconstrictive effects and renal toxicity. Major efforts being undertaken at present by industry and research groups give reason to hope, however, that the concept of modified Hb solutions as oxygen carriers will be realized in the foreseeable future.

Animals↗

Clinical significance of mean circulatory filling pressure and cardiac preload under anesthesia.

The circulatory effects of a rapid infusion of plasma substitute with intravenous administration of nitroglycerine (TNG) were investigated in low pressure systems of anesthetized patients by measuring various hemodynamic parameters. Measurements were made when the systolic blood pressure reached 70-80% of the control value after intravenous administration of TNG at 1-2 microg/kg/min and a 3.5% modified gelatin solution (Haemaccel) at a rate of 0.5 ml/kg/min. After the TNG was administered, the mean circulatory filling pressure (Pms) decreased, and the venous to arterial capacitance ratio (CV/CA) increased; however, they returned to control values after a rapid Haemaccel infusion. Changes in the pressure gradient between the X and Y valley of the right atrial pressure wave decreased to 70 +/- 14% of the control value when TNG was given and recovered to 106 +/- 22% by infusion. Pulmonary vascular resistance (PVR) decreased to 70 +/- 24% of the control value when TNG was administered and was restored to 96 +/- 40% by a rapid infusion. In the left ventricle, the mean velocity of myocardial circumferential fiber shortening (VCF) decreased in all cases when TNG was given and it recovered by a rapid infusion. In the right ventricle, VGF did not always decrease, and in a few case increased, but all cases recovered by a Haemaccel rapid infusion. We conclude that the augmentation of the right ventricular preload reserve is achieved by administration of TNG and infusion of a plasma substitute.

Journal Article↗

Clinical experience with 120,000 units of modified fluid gelatin.

We briefly review 20 years of clinical experience with 120.531 units of a 4% modified fluid gelatin as a plasma substitute. Its Mn is 22.500. The initial intravascular volume effect equals that of 4% albumin; the t0,5 of this effect is about 4 hours. It has no dosage-related side effects and specifically does not impair surgical hemostasis in volumes up to 10-15 litres within 24 hours. During the last 5 years, it has become an essential element of a blood component program, which has proven to be therapeutically satisfactory and logistically advantageous. More than 1000 patients have received more than 2000 ml within 24 hours as a part of massive transfusions. The incidence of serious anaphylactoid reactions has been 1 per 13,400 units, but only one fatality has occurred. At least one out of 7 "gelatin" reactions cannot have been caused by the colloid itself. These incidents were presumably due to trace contaminants. When compared to dextran, it appears that this gelatin is more prone to cause harmless cutaneous reactions, but less likely to induce severe cardiovascular incidents.

Blood Transfusion↗