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Safety of iron dextran in total parenteral nutrition: a case report.

Parenteral iron, in the form of intramuscular injection or intravenous infusion of iron dextran, is commonly used to treat iron deficiency. Constitutional symptoms, anaphylaxis, and rarely death are risks associated with the use of iron dextran for this purpose. However, iron supplementation of TPN solutions to meet daily requirements can be accomplished safely. We propose that iron dextran added to TPN is well tolerated by patients because the amounts employed are small and the infusion times are long. To illustrate, we present a case where rapid administration of parenteral iron was associated with allergic type symptoms. Inclusion of daily requirements of iron in the TPN solution prior to and subsequent to this reaction did not elicit symptoms.

Adult↗

Conformational studies of dextran [alpha-(1----6)-D-glucan].

A theoretical conformational study of dextran, a (1----6)-linked alpha-D-glucan polysaccharide, has been made to allow n explicit comparison with earlier results on pustulan, the corresponding (1----6)-linked beta-D-glucan. The nonbonded, torsional and hydrogen bond contributions to potential energy were calculated as a function of rotational angles phi, psi, and omega. The (phi, psi, omega)-space of the disaccharide and of helices contain many local energy minima with very small energy differences. A comparison of (1----6)-alpha-D-glucans with (1----6)-beta-D-glucans indicates significantly differences in conformational behavior. Specifically, our results shed light on the fact that dextran does not gel, whereas pustulan does. The difference in tendency to gel may be related to the fact that dextran has no particularly favored conformations with structural regularity whereas pustulan does.

Carbohydrate Conformation↗

Complication of oliguric acute renal failure in patients treated with low-molecular weight dextran.

Acute renal failure (ARF) is a well-documented but infrequent complication in patients treated with low-molecular weight dextran (LMWD). We herein report 3 cases of oliguric ARF following the administration of dextran-40. One case developed ARF totally after 1.200 g of LMWD administration. In contrast, two cases having increased serum creatinine developed oliguria despite the acceptable therapeutic doses (totally 450 and 650 g). Contrast media was also co-administered in these patients. Plasma exchange (PE), double filtration plasmapheresis (DFPP), or continuous hemodiafiltration (CHDF) but not hemodialysis (HD) reduced circulating dextran concentrations by 35-44% during a single session. All patients completely recovered from ARF by 14-32 days after the treatment. Our cases suggested that radiocontrast could predispose to the development of LMWD-induced ARF especially in patients having pre-existing renal dysfunction. In addition, PE, DFPP and CHDF afforded a beneficial effect for removing accumulated LMWD from the circulation.

Acute Kidney Injury↗

Total dose infusion iron dextran therapy in predialysis chronic renal failure patients.

BACKGROUND: Intravenous iron therapy is now the standard modality of iron supplementation in hemodialysis patients, but its role in predialysis chronic renal failure patients is less well established. The efficacy and safety of intravenous iron dextran as a total dose infusion in predialysis chronic renal failure patients, not receiving erythropoietin was assessed in this study. METHODS: Fifty-six predialysis chronic renal failure patients with anemia, not receiving erythropoietin were included in the study, after obtaining informed consent. Hemoglobin, serum creatinine, creatinine clearance rate and serum ferritin were assessed in all the patients at baseline. Iron dextran in a dose of 1 g dissolved in 500 mL normal saline was administered to all patients as a total dose infusion over 6 h after a prior test dose. Patients were kept in hospital under observation for at least 24 h. All the parameters were repeated in all the patients at 12 weeks and in 21 patients at 1 year. RESULTS: The mean hemoglobin (g/dL) in the patients at baseline and at 12 weeks was 8.28 +/- 0.57 and 9.22 +/- 0.44 respectively (p < 0.001). The mean serum ferritin (ng/mL) increased from 29.73 +/- 9.38 at baseline to 218.43 +/- 15.66 at 12 weeks (p < 0.00001). The mean ferritin value in the 21 patients at 1 year was 136.5 +/- 23.4 (p < 0.01). There were no major adverse events and only minor side effects were observed in 4.9% patients. CONCLUSION: Iron dextran as a total dose infusion corrects anemia in predialysis patients and is an effective method to replenish iron stores. The effect on serum ferritin are evident even at 1 year after the total dose infusion.

Adolescent↗

Permeability of intestinal capillaries. Pathway followed by dextrans and glycogens.

The pathway followed by macromolecules across the wall of visceral capillaries has been studied by using a set of tracers of graded sizes, ranging in diameter from 100 A (ferritin) to 300 A (glycogen). Polysaccharide particles, i.e. dextran 75 (mol wt approximately 75,000; diam approximately 125 A), dextran 250 (mol wt 250,000; diam approximately 225 A), shellfish glycogen (diam approximately 200 A) and rabbit liver glycogen (diam approximately 300 A), are well tolerated by Wistar-Furth rats and give no vascular reactions ascribable to histamine release. Good definition and high contrast of the tracer particles were obtained in a one-step fixation-in block staining of the tissues by a mixture containing aldehydes, OsO(4) and lead citrate in phosphate or arsenate buffer, pH 7.4, followed by lead staining of sections. The glycogens and dextrans used move out of the plasma through the fenestrae and channels of the endothelium relatively fast (3-7 min) and create in the pericapillary spaces transient (2-5 min) concentration gradients centered on the fenestrated sectors of the capillary walls. The tracers also gained access to the plasmalemmal vesicles, first on the blood front and subsequently on the tissue front of the endothelium. The particles are temporarily retained by the basement membrane. No probe moved through the intercellular junctions. It is concluded that, in visceral capillaries, the fenestrae, channels, and plasmalemmal vesicles, viewed as related parts in a system of dynamic structures, are the structural equivalent of the large pore system.

Animals↗

The permeability of glomerular capillaries to graded dextrans. Identification of the basement membrane as the primary filtration barrier.

Graded dextrans have been used as tracers to identify the primary permeability barrier(s) to macromolecules among the structural elements (endothelium, mesangium, basement membrane, epithelium) of the glomerular capillary wall. Three narrow-range fractions of specified molecular weights and Einstein-Stokes radii (ESR) were prepared by gel filtration: (a) 32,000 mol wt, ESR = 38 A; (b) 62,000 mol wt, ESR = 55 A; and (c) 125,000 mol wt, ESR = 78 A. These fractions are known to be extensively filtered, filtered in only small amounts, and largely retained, respectively, by the glomerular capillaries. Tracer solutions were infused i.v. into Wistar-Furth rats, and the left kidney was fixed after 5 min to 4 h. The preparations behaved as predicted: initially, all three fractions appeared in the urinary spaces, with 32,000 > 62,000 >> 125,000. The smallest fraction was totally cleared from the blood and urinary spaces by 2.5 h, whereas the intermediate and largest fractions were retained in the circulation at high concentrations up to 4 h. With all fractions, when particles occurred in high concentration in the capillary lumina, they were present in similarly high concentrations in the endothelial fenestrae and inner (subendothelial) portions of the basement membrane, but there was a sharp drop in their concentration at this level-i.e., between the inner, looser portions of the basement membrane and its outer, more compact portions. With the two largest fractions, accumulation of particles occurred against the basement membrane in the mesangial regions with time. No accumulation was seen with any of the fractions in the epithelial slits or against the slit membranes. Dextran was also seen in phagosomes in mesangial cells, and in absorption droplets in the glomerular and proximal tubule epithelium. It is concluded that the basement membrane is the main glomerular permeability barrier to dextrans, and (since their behavior is known to be similar) to proteins of comparable dimensions (40,000-200,000 mol wt). The findings are discussed in relation to previous work using electron-opaque tracers to localize the glomerular permeability barrier and in relation to models proposed for the functions of the various glomerular structural elements.

Animals↗

Structural correlates of cross-reactive and individual idiotypic determinants on murine antibodies to alpha-(1 leads to 3) dextran.

For the first time V-region amino acid sequence differences have been correlated with the expression of cross-reactive and individual idiotypes through an analysis of 12 dextran-binding proteins. This correlation has been possible because of the apparent sequence identity of the corresponding lambda chains. Expression of a cross-reactive idiotype was localized to two residues and/or a carbohydrate in the second hypervariable region of the heavy chain. Two individual idiotypes correlate with the two amino acids within the third hypervariable region that comprises the D segment of the dextran-binding proteins. These results demonstrate that idiotype reagents can recognize two amino acid differences within V and D segments of classical variable regions. In anti-dextran antibodies, cross-reactive idiotypes involve V-region determinants, whereas individual idiotype determinants correlate with D-segment variation.

Amino Acid Sequence↗

Sentinel lymph node mapping in melanoma with technetium-99m dextran.

PURPOSE: The aim of this work is to evaluate the capability of Tc99m B Dextran as a lymphoscintigraphic agent in the detection of the sentinel node in skin lesions. MATERIALS AND METHODS: Forty-one patients with melanomas (39) and Merkel cell tumors (2) had perilesional intradermal injection of Tc99m-Dextran 2 hours before surgery. Serial gamma camera images and a handheld gamma probe were used to direct sentinel node biopsy. RESULTS: In 39/41 patients, lymph channels and 52 sentinel nodes (one to three sentinel nodes/patient) could be visualized. In one patient, with a dorsal melanoma, no lymph channels or lymph nodes could be demonstrated on the images and only minimal radioactivity was found in the regional nodes with the probe. Another patient with a facial lesion failed to demonstrate lymph channels or nodes. No adverse reactions were observed. CONCLUSION: Tc99m-Dextran provided good definition of lymph channels and sentinel node localization, without the risks related to the use of potentially hazardous labeled materials of biological origin.

Adolescent↗

Effects of haemodilution with fluorocarbons or dextran on oxygen tensions in the acutely ischaemic myocardium.

The effect of haemodilution with dextran or with oxygen transporting fluorocarbons (Fluosol-DA 20%) on myocardial oxygen tension (PmO2) during experimental myocardial ischaemia was studied in pigs. Polarographic oxygen microelectrodes were introduced 3 mm to the left ventricle wall and the distal one-third of the left anterior descending coronary artery (LAD) was occluded. Anaesthesia was maintained with 0.5% halothane in oxygen to ensure maximal oxygen content of the fluorocarbons. The animals were divided into three groups of five animals each. In group I no treatment was given and in groups II and III, after bleeding 20 ml kg-1, haemodilution was performed with Fluosol-DA 20% or 5% dextran respectively. Occlusion of the LAD caused no significant changes in cardiovascular vascular variables and only in group III (dextran) were significant effects of haemodilution observed. LAD occlusion caused highly significant decreases in PmO2. After haemodilution, PmO2 in the Fluosol group II (in contrast to groups I and III) was no longer significantly different from pre-occlusion values. After 5 h of occlusion, mean PmO2 in this group had returned to 92.2% of the pre-occlusion values, whereas in groups I and III it was 27.8% and 33.7%, respectively.

Animals↗

Influence of dextran on the absorption of adrenaline-containing lignocaine solutions: a protective mechanism in local anaesthesia.

The effect of adding 6% dextran to a lignocaine solution containing adrenaline was studied in 27 neurosurgical patients during modified neuroleptanaesthesia. Before trepanation they received infiltration anaesthesia of the scalp at the site of the proposed operation. For a period of 1 h following injection plasma concentrations of adrenaline were measured by high pressure liquid chromatography and serum concentrations of lignocaine by gas chromatography. The addition of dextran caused a significant reduction in the absorption of both adrenaline and lignocaine from the injection site. It is concluded that the dextran adjuvant constitutes a protective mechanism against toxic systemic side effects in local anaesthesia using adrenaline-containing anaesthetic solutions. This effect is particularly significant in patients with pre-existing cardiovascular disease and when local anaesthetic solutions are used in combination with volatile anaesthetics.

Absorption↗

Iron is well absorbed by healthy adults after ingestion of double-fortified (iron and dextran-coated iodine) table salt and urinary iodine excretion is unaffected.

Severe deficiencies of iron (Fe) and iodine (I) affect more than one third of the world's population. A table salt, fortified with I and Fe, would be useful in areas in which anemia and goiter coexist. However, interactions between the two minerals have prevented their simultaneous use as fortificants. A method has been developed to coat I with dextran such that after spraying onto table salt, Fe and I do not interact. Our objective was to determine the absorption of Fe and the urinary excretion of I from table salt when provided in meals designed to significantly inhibit or enhance Fe absorption. Subjects (n = 16) ingested Fe-enhancing and Fe-inhibiting meals containing 5 g of table salt with 0.39 micromol dextran-coated I as potassium iodide and 1 mg of Fe (ferrous fumarate labeled with 59Fe) per gram of salt. Subjects also received a reference dose of 3 mg of ferrous fumarate labeled with 59Fe to "correct" for interindividual variation in iron absorption at a later date. Measured by whole-body counting, Fe-absorption from the Fe-enhancing meal (36.2 +/- 12.0%, corrected; 13.5 +/- 13.8% uncorrected) was significantly higher than that from the Fe-inhibiting meal (7.4 +/- 11.3%, corrected; 4.0 +/- 8.4%, uncorrected) (P < 0.0001). Urinary excretion of iodine at baseline and postingestion were not significantly different (0.89 +/- 0.5 vs. 1.06 +/- 0.39 micromol/L, P < 0.47) and were within the normal range. We conclude that Fe was well absorbed but influenced by the composition of the meal and that urinary excretion of iodine was maintained in the normal range with dextran-coated iodine.

Absorption↗

High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment.

Using a plasmid containing the bacterial chloramphenicol acetyl transferase gene, we have assayed for transient expression of DNA introduced into mouse L cells by a variety of transfection conditions. High efficiency uptake and expression of this foreign DNA have been achieved by modifying the DEAE dextran mediated transfection procedure of McCutchan and Pagano (1) to include a shock with either dimethyl sulfoxide or glycerol. Inclusion of the shock step can increase expression of the transfected gene a surprising approximately 50 fold. With plasmid constructs that do not replicate after transfection, we can readily detect CAT activity in an overnight autoradiographic exposure from less than 0.1% of an extract from a 60 mm dish of transfected cells. We have determined the amounts of DNA, the amount and time course of DEAE-dextran and dimethyl sulfoxide treatments, the effects of additional DNA, and the time after transfection which yield maximal expression. Overall, this transfection protocol using DEAE-dextran coupled to a shock treatment is simple, straightforward, and gives consistently high levels of expression of the input DNA.

Acetyltransferases↗

Permeability of the primary decidual zone in the rat uterus: studies using fluorescein-labeled proteins and dextrans.

The primary decidual zone (PDZ) is a transitory avascular region of transformed fibroblasts surrounding the luminal epithelium at the implantation site. Since this zone may restrict the passage of immunoglobulins, cells, nutrients, and other substances from maternal blood to the epithelium and embryo from Days 6 to 8 of pregnancy, it was of interest to study its permeability to blood-borne tracers. Fluorescein isothiocyanate (FITC)-labeled macromolecules were administered i.v. on Days 6 to 9 of pregnancy. The tracers included dextran (17 kDa), horseradish peroxidase (40 kDa), ovalbumin (45 kDa), dextran (66 kDa), bovine serum albumin (BSA: 66 kDa), dextran (156 kDa), bovine immunoglobulin G (IgG; 160 kDa), and apoferritin (450 kDa). Ten minutes after administration on Days 6 or 7, FITC-labeled tracers of molecular masses of 45 kDa or less were localized in the intercellular spaces of the PDZ and in the blastocyst in small amounts. Tracers with molecular masses of 66 kDa were not detected in these regions up to 1 h after administration but were present in small amounts at 5 h. The 156 kDa and 160 kDa tracers were absent or present only in very small amounts in the PDZ and blastocyst up to 7 h after injection and apoferritin was completely absent at this time. By Day 9 the PDZ had regressed and maternal blood spaces were present adjacent to Reichert's membrane. One hour after administration on Day 9, large quantities of labeled BSA, IgG, and apoferritin appeared in the yolk sac endoderm but not in the underlying embryonic cells. These observations indicate that the PDZ is selectively permeable to blood-borne tracers on Days 6 and 7 of pregnancy, with permeability decreasing with increasing molecular mass. By restricting the passage of high molecular weight substances such as immunoglobulins, microorganisms, and immunocompetent cells, the PDZ may serve a protective function for the embryo, which is no longer protected by the uterine epithelium and has not yet fully developed its own protective layers, especially the yolk sac and Reichert's membrane.

Animals↗

Case report: dextran-induced acute anuric renal failure.

Acute renal failure is an infrequent adverse reaction following the administration of dextran-40. We report a case of anuric acute renal failure in a 59-year-old female following the administration of 90 gm of dextran-40 and radiocontrast. An increased risk secondary to radiocontrast-induced ischemia is discussed in relationship to the pathogenesis of the dextran-induced acute renal failure. In addition, plasmapheresis is demonstrated to be of potential therapeutic benefit.

Acute Kidney Injury↗

Hypertonic saline dextran does not increase cardiac contractile function during small volume resuscitation from hemorrhagic shock in anesthetized pigs.

Small volumes of hypertonic saline dextran (10% of shed blood volume [SBV] restore cardiac output (CO) and increase arterial pressure in hemorrhagic shock. Besides rapid expansion of plasma volume, a positive inotropic effect has been proposed as an additional mechanism for the immediate onset of the cardiovascular response. This study compares the effects of 7.2% saline/10% dextran 60 (HSDex, n = 8) and normal saline (NS; n = 6) on central hemodynamics and cardiac contractility assessed by end-systolic elastance (Ees; conductance technique) and segmental preload recruitable stroke work (sPRSW; sonomicrometry). In anesthetized open chest pigs (28 +/- 1 kg, mean +/- SEM) shock was induced by blood withdrawal (40% of blood volume) to maintain mean arterial pressure (MAP) at 45 mm Hg for 75 min. Resuscitation was started by bolus infusion (2 min) of either HSDex (10% of SBV) or the identical sodium load of NS (80% of SBV); 30 min later both groups received 6% dextran (10% of SBV). Hemorrhagic shock reduced CO (-45%) and left ventricular end-diastolic volume (Ved; -70%) while Ees increased (NS:2.2 +/- 0.4 to 7.5 +/- 1.8 mm Hg/mL, P < 0.05; HSDex: 1.9 +/- 0.2 to 9.1 +/- 2.6 mm Hg/mL, P = 0.085). Within 5 min after infusion of either solution CO returned to baseline values and MAP (NS +55%, HSDex +64%) and Ved (+100%) increased. Neither HSDex nor NS increased Ees above shock levels (NS, 8.7 +/- 4.9 mm Hg/mL; HSDex, 7.3 +/- 2.6 mm Hg/mL) and no group differences occurred in other measurements of contractility (dP/dt40,sPRSW). Plasma osmolality increased to 328 +/- 3 mOsmol/kg with HSDex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of rate and volume of infusion on the kinetics of 0.9% saline and 7.5% saline/6.0% dextran 70 in sheep.

UNLABELLED: We examined whether volume kinetic variables obtained during infusion of a short bolus of 0.9% saline (NS) or 7.5% saline/6.0% dextran 70 (HSD) predict the dilution-time curve resulting from a 20-min infusion of the same fluid. Each of six conscious, splenectomized sheep (mean body weight, 36 +/- 3 kg), on 4 different days, in a random order, received each of 4 IV boluses: NS at a rate of 1.2 mL. kg(-1). min(-1) over 5 min or 20 min or 4.0 mL/kg of HSD over 2 min or 20 min. One, 2, and 3-volume kinetic models were fitted to the dilution of the arterial hemoglobin concentration and the urinary excretion as sampled during 180 min. The maximum dilution of arterial plasma at the end of the 5-min and 20-min infusions of NS was approximately 10% and 22%, respectively, and after the 2-min and 20-min infusions of HSD, maximum dilution was 24% and 21%, respectively. The median absolute performance error was virtually identical when the mean variable estimates from the 5-min infusion of NS were used to predict the individual dilution-time curves of the 5-min (mean, 0.027 dilution units) and 20-min (mean, 0.027) infusions and when the 2-min infusion of HSD was used to predict the dilution during the individual 2-min (mean, 0.050) and 20-min infusions (mean, 0.047). Computer simulations indicated that the difference at the end of infusion between the volume effects of NS and HSD is larger after longer infusions. We concluded that the volume kinetic variables obtained during a short infusion can be used to predict the outcome of a longer one, even if the longer infusion also delivers a larger volume. IMPLICATIONS: Kinetic analysis of a short infusion of 7.5% saline/6% dextran or 0.9% saline accurately predicts the effects of a longer infusion of the same volume (7.5% saline/6% dextran) or of a larger volume (0.9% saline).

Animals↗

Fluid replacement monitoring: effect of dextran overload, norepinephrine drip, and positive pressure ventilation on systemic arterial, right atrial pulmonary wedge, and left atrial pressures in dogs.

The effects of dextran overload, norepinephrine drip and positive pressure ventilation upon right atrial, pulmonary wedge, left atrial and systemic arterial pressures were studied in 15 dogs. Rapid intravenous infusion of Dextran 70 invariably produced a marked and statistically significant (p < .001) rise in right atrial, pulmonary wedge and left atrial pressures. The rise in left atrial pressure invariably exceeded the rise in right atrial pressure, and the difference in maximum pressures averaged 10.8 mm Hg (p < .001). Thus acute fluid overload and pulmonary edema can be produced by rapid infusion of colloid solution in the absence of a marked rise in right atrial pressure, a point of considerable clinical importance. The rapid infusion of dextran produced a rise in systemic arterial blood pressure in all dogs so studied, though this rise was mild in some animals. This finding may explain in part the hypertension exhibited by patients in the recovery room who may have been overtransfused. A norepinephrine drip usually produced an increase in right atrial, wedge, left atrial and systemic arterial blood pressure (p < .01). When there was a significant rise in right atrial pressure and left atrial pressure, the maximum increase in left atrial pressure was always greater than the maximum increase in right atrial pressure (p < .005). This finding again emphasizes the fact that blood transfusion requirements cannot always be accurately assessed on the basis of right and left atrial pressure measurements when a vasopressor agent is being administered. Positive pressure ventilation increased both right and left atrial pressures, as expected. It was again confirmed that pulmonary wedge pressure, as measured with the Swan-Ganz catheter, is approximately equal to left atrial pressure over a wide range of induced variations. The Swan-Ganz catheter, introduced at the bedside in the intensive care unit when necessary, can provide highly useful information regarding left atrial pressure and left ventricular end-diastolic pressure.

Animals↗

Experimental acute pancreatitis: the changes in pancreatic oxygen consumption and the effect of Dextran 40.

A canine model was devised to measure the oxygen consumption of the pancreas in experimentally induced pancreatitis. Over the 120 minute investigation period the oxygen consumption fell by 63% in the presence of a diminishing pancreatic blood flow and constant arteriovenous percentage saturation across the pancreas. Dextran 40 has been previously shown to maintain the pancreatic circulation. Accordingly a second group of dogs was treated with Dextran 40 (1.5 ml/kg) 60 minutes after induction of the pancreatitis. This produced a significant increase in the pancreatic oxygen consumption and widening of the arteriovenous difference. Dextran 40 appears to reverse the hypoxia of the pancreas noted in acute experimental pancreatitis.

Acute Disease↗