Microgravimetric Technique Research Articles

The Relationship Between Different Bench Test Methodologies and Accuracy of Insulin Infusion Pumps: A Systematic Literature Review

Diabetes technology has rapidly evolved, and insulin infusion pumps (IIPs) have gained worldwide acceptance in diabetes care. The safety of medical equipment is highly discussed, imposing complex challenges in its use. The accuracy of IIPs can be determined through laboratory tests, generally following the IEC 60601-2-24 protocol. Studies have evaluated the accuracy and precision of IIPs, and there are discrepant results. So, we conducted a Systematic Literature Review to assess the methodologies used to evaluate the accuracy of IIPs, organizing the findings in a compiled perspective. The methodology was based on Kitchenham and Biolchini guidelines, and when possible it was carried out the Bayesian meta-analyses to compare the accuracy of IIPs. Most studies used the microgravimetric technique to evaluate the device accuracy, and some proposed adaptations for the standard protocol. The variation of results was recurrent, and the establishment of a protocol, especially to evaluate patch pumps, is necessary. The present study gives enough data to understand the scenario of the IIPs evaluation, as well as the different protocols that can be explored for its evaluation. This highlights the need for a reliable, practical, and low-cost methodology to assist the evaluation of IIPs.

Cation exchange modification of clinoptilolite –thermodynamic effects on adsorption separations of carbon dioxide, methane, and nitrogen

Abstract This study details an experimental analysis of the thermodynamics of adsorption equilibrium behaviour of pure CO2, CH4, and N2 gases on raw, Fe3+, Ca2+, and Cs+ cation exchanged clinoptilolite. Equilibrium adsorption isotherms were experimentally determined for CO2, CH4, and N2 at three different temperatures ranging from 303 K up to 363 K, at pressures up to 8.0atm using the microgravimetric technique. Kinetic adsorption uptake data was measured at different temperatures for CH4 and N2 gases, and the results were compared for raw and Ca2+ clinoptilolite. Heat of adsorption values were calculated for all three gases on the studied clinoptilolite samples using the chromatographic method. These results were compared to the isosteric adsorption enthalpies determined from the adsorption isotherms at different temperatures. The isosteric heat of adsorption was the highest for CO2 followed by CH4, and N2. Temperature dependent Sips, Toth, and Dual-Site Langmuir isotherm models were fitted with experimental data and selectivity factor values were calculated for CO2/CH4 and CH4/N2 gas separations using the regressed isotherm models. Ca2+ clinoptilolite shows the best potential for CO2/CH4 separations due to its high selectivity. However, higher temperatures are needed in order to compensate for the slow kinetic behaviour. For CH4/N2 separations, Fe3+ clinoptilolite selectivity displays both high values and less variability compared to Cs+ clinoptilolite over a broader range of temperatures and pressures.

Microgravimetric and ground penetrating radar geophysical methods to map the shallow karstic cavities network in a coastal area (Marina Di Capilungo, Lecce, Italy)

The coastal area Marina di Capilungo located ~50 km south-west of Lecce (Italy) is one of the sites at greatest geological risk in the Salento peninsula. In the past few decades, Marina di Capilungo has been affected by a series of subsidence events, which have led in some cases to the partial collapse of buildings and road surfaces. These events had both social repercussions, causing alarm and emergency situations, and economic ones in terms of the funds for restoration.With the aim of mapping the subsurface karstic features, and so to assess the dimensions of the phenomena in order to prevent and/or limit the ground subsidence events, integrated geophysical surveys were undertaken in an area of ~70 000 m2 at Marina di Capilungo. Large volume voids such as karstic cavities are excellent targets for microgravity surveys. The absent mass of the void creates a quantifiable disturbance in the earth’s gravitational field, with the magnitude of the disturbance directly proportional to the volume of the void. Smaller shallow voids can be detected using ground-penetrating radar (GPR). Microgravimetric and GPR geophysical methods were therefore used. An accurate interpretation was obtained using small station spacing and accurate geophysical data processing. The interpretation was facilitated by combining the modelling of the data with the geological and topographic information for explored caves. The GPR method can complement the microgravimetric technique in determining cavity depths and in verifying the presence of off-line features and numerous areas of small cavities, which may be difficult to be resolved with only microgravimetric data. However, the microgravimetric can complement GPR in delineating with accuracy the shallow cavities in a wide area where GPR measurements are difficult. Furthermore, microgravity surveys in an urban environment require effective and accurate consideration of the effects given by infrastructures, such as buildings, as well as those given by topography, near a gravity station. The acquired negative anomaly in the residual Bouguer anomalies field suggested the presence of possible void features. GPR and modelling data were used to estimate the depth and shape of the anomalous source.

A new experimental method for determination of solubility and hyper-solubility of hygroscopic solid

A microgravimetric technique for the determination of solubility, c°, of hygroscopic solid is proposed. The method allows the determination of the critical concentration of supersaturated solution, c⁎, where spontaneous nucleation of the solid phase takes place. The two concentrations, c° and c⁎, delimit the metastable domain of supersaturated solutions wherein growth of crystals is realisable. Ammonium nitrate is used as a model of hygroscopic solid. The kinetics of absorption of water vapor is followed by high precision microbalance (Dynamic Vapor Sorption). Powder sample is placed in an atmosphere of constant temperature and of relative humidity superior to the critical relative humidity while mass of absorbed water vapor is monitored continuously. As long as solid phase is present in the sample holder, the rate of absorption is constant and determined by the imposed relative humidity. The absorption of water continues even after all solid is dissolved, but, due to continuous dilution of the obtained solution, by continuously decreasing rate. The change of kinetics of water sorption is used as an indicator for the determination of the solid/liquid equilibrium concentration (or solubility), c°. The concentration c⁎ is determined by subsequently performed measurements but at relative humidity lower then the critical relative humidity for a given temperature: water evaporates at continuously decreasing rate because the concentration of solute in solution increases; highly supersaturated solutions can be obtained in such a way. When finally the solid phase appears in the supersaturated solution evaporation suddenly accelerates; this change of regime is used for the determination of the critical supersaturation concentration, c⁎. The evaporation accompanied by growth of crystals proceeds until all water is evacuated from the sample. In present paper we compare thus obtained solubility curve to the known literature data for ammonium nitrate.

Magnetic field effects on electrochemical metal depositions

This paper discusses recent experimental and numerical results from the authors' labs on the effects of moderate magnetic (B) fields in electrochemical reactions. The probably best understood effect of B fields during electrochemical reactions is the magnetohydrodynamic (MHD) effect. In the majority of cases it manifests itself in increased mass transport rates which are a direct consequence of Lorentz forces in the bulk of the electrolyte. This enhanced mass transport can directly affect the electrocrystallization. The partial currents for the nucleation of nickel in magnetic fields were determined using an in situ micro-gravimetric technique and are discussed on the basis of the nucleation model of Heerman and Tarallo. Another focus of the paper is the numerical simulation of MHD effects on electrochemical metal depositions. A careful analysis of the governing equations shows that many MHD problems must be treated in a 3D geometry. In most cases there is a complex interplay of natural and magnetically driven convection.

Adsorption and diffusion of cyclopentane in silicalite-1: a thermodynamic and kinetic study

The adsorption isotherm, differential thermal gravimetry (DTG), thermal gravimetry (TG), diffusion and thermodynamic parameters of cyclopentane at various adsorption coverages have been investigated using microgravimetric technique over a range of temperature. The differences in equilibrium adsorption capacity and in diffusion coefficient at different temperature are discussed in terms of the characteristics of silicalite-1 and the features of cyclopentane molecule. The heat of sorption Qst varies significantly with sorption coverage indicating that the adsorption and diffusion mechanism is complex. The dependences of thermodynamic properties like free energy change (ΔG) and entropy change (ΔS) on sorption coverage show a sharp decrease and increase suggesting that the adsorption sites of the silicalite-1 are not energetically uniform to cyclopentane. Two desorption peaks in the DTG and TG curves suggest that two heterogenous binding sites surely exist in silicalite-1 to cyclopentane.

Modelling of vapour sorption in polar materials: Comparison of Flory–Huggins and related models with the ENSIC mechanistic approach

This work focuses on the analysis of organic vapour sorption in polymer systems strongly deviating from ideality. The sorption of three different types of organics (i.e. alcohol, ether, ester) in polyurethaneimide block copolymers has been investigated using a microgravimetric technique over the entire activity range. For all the polyurethaneimides, sorption increases in the following order: ETBE<EtOH<AcOEt. A further analysis in terms of the Flory–Huggins (FH) theory generally shows a great discrepancy between experimental and calculated sorption values. This quasi-systematic failure could be ascribed to a fairly strong dependence of FH interaction parameter χ towards penetrant concentration, which cannot be accounted for by the FH theory. A theoretical modification of the FH theory, previously reported by Koningsveld and Kleintjens to account for the variation by a three-parameter law, was shown to be really efficient for sorption modeling over the entire activity range. Despite a systematic divergence for the very low sorption levels, an empirical modification of the FH theory using a power law χ= aφ b could also be an interesting alternative which requires only two parameters for a fairly good modeling for activities higher than 0.1–0.2. Considering the sorption phenomenon as a mechanical anisotropic process, the recent ENSIC approach, reported by Favre et al., proved its striking efficiency allowing the sorption modelling of all the sorption isotherms with a mean correlation coefficient R=0.9983.

BETA-BLOCKADE AS AN ALTERNATIVE TO CARDIOPLEGIC ARREST DURING CARDIOPULMONARY BYPASS IN DOGS

S115 Introduction: As an alternative to cardioplegic arrest, cardiac surgical conditions have been reported using beta-blocker induced minimal myocardial contraction (MMC) during cardiopulmonary bypass. [1] The technique of MMC involves the use of high dose intravenous esmolol to suppress myocardial chronotropy and inotropy sufficiently to provide cardiac surgical conditions. The purpose of this study was to compare conventional crystalloid cardioplegic arrest (CA) to MMC in terms of ischemia avoidance, myocardial edema formation, and cardiac function. Methods: All procedures were approved by The University of Texas Animal Welfare Committee. Twelve dogs were placed on cardiopulmonary bypass. Six dogs were subjected to crystalloid cardioplegic arrest for two hours. Surgical conditions were produced in the other 6 dogs for 2 hours with intravenous esmolol avoiding aortic clamping and cardioplegia. Arterial and coronary sinus lactate concentrations were determined as a gauge of myocardial ischemia. Myocardial water content was determined from endomyocardial biopsies by a microgravimetric technique using a linear density gradient. Preload recruitable stroke work (PRSW), a measure of contractility, was calculated using left ventricular pressure-volume loops derived from sonomicrometry and micromanometry. Results: Significant lactate washout was demonstrated following cardioplegic arrest but not following MMC. Myocardial water content was significantly less during and after MMC compared to cardioplegic arrest (Table 1). Preload recruitable stroke work was decreased compared to baseline in both groups (P<0.05).Table 1: Myocardial Water Content (%)Discussion: In contrast to a previous study involving one hour of MMC, ventricular function was decreased to the same extent as the cardioplegic arrest group following two hours of MMC. This was attributed to the accumulation of ASL-8123, the primary metabolite of esmolol which possesses beta-antagonist properties. While post-bypass ventricular function is similar in both groups, MMC appears to be superior in terms of ischemia avoidance and myocardial edema minimization.

Langmuir films of Fc binding receptors engineered from protein A and protein G as a sublayer for immunoglobulin orientation

The paper describes the production and immobilization of Langmuir monolayers of recombinant proteins A and G and the chimeric protein A G . The films were used for the immobilization of IgG molecules on the solid supports. Making use of the high affinity of the proteins A and G to the Fc fragments, the orientation technique provides the IgG position with the Fab fragments directed outward, capturing the antigen in the mobile phase. The films of binding receptors were characterized by ellipsometry and nanogravimetry and its IgG binding capacities were tested by fluorescent assays. The immunological activity of IgG films organized by means of receptor sublayers was studied by the microgravimetric technique. The sensitivity of the monolayer of rabbit anti-mouse IgG oriented with protein A sublayer towards mouse IgG is in the range of 10–100 pM.

Age-Related Changes in Rat Interstitial Matrix Hydration and Serum Proteins

Measurements of effects of age-related changes on loose connective tissue protein concentrations and water are lacking. Tissue hydration is an important determinant of tissue protein diffusion coefficients and hydraulic conductivity. Sprague-Dawley rats (ages 11, 30, 57, and 89 wk) were anesthetized. Blood and mesenteric tissue samples were taken. Tissue water content was determined by microgravimetric technique. Protein content was determined by electrophoresis. Tissue hydration decreased 18% between 11 and 89 wk with one-half the fall occurring between 57 and 89 wk. Tissue albumin concentration decreased 37% between 11 and 89 wk. Serum albumin increased 22% between 11 and 30 wk and then decreased by 37% to 1.4 g/dl in 89-wk rats. Serum total protein concentration increased by 13% between 11 and 89 wk, whereas tissue total protein concentration decreased 30% with age to 1.9 g/dl at 89 wk. The results suggest that age-related tissue dehydration is due, in part, to a shift in the colloid osmotic pressure components of Starling equilibrium favoring fluid reabsorption.

Development of gas standards from solid 1,4-dichlorobenzene

For over fifteen years the National Institute of Standards and Technology (NIST) has been preparing gas standards containing volatile organic compounds at sub μmol/mol (ppm) concentrations. These standards have been prepared using organic compounds that are either gases or liquids at room temperature. A microgravimetric technique was developed previously to prepare standards containing these compounds in treated aluminum gas cylinders using a one step dilution. Requests were received to prepare gas standards containing the compound 1,4-dichlorobenzene. These requests posed a major problem in that 1,4-dichlorobenzene is a solid at room temperature. Research was undertaken, using the microgravimetric procedure, to determine if it was feasible to prepare gas standards from solid phase compounds. In the first stage of research the liquid phase compound 1,2-dichlorobenzene, previously studied at NIST in gas mixtures, was used as an internal standard. Results from analyses of a prepared gas standard showed that the response factor on a gas chromatograph flame-ionization detector for 1,3-dichlorobenzene was 3% less than that for 1,2-dichlorobenzene. Additional analyses using liquid solution standards also showed a lower response factor for 1,3-dichlorobenzene of 2.9% on average. It was assumed that 1,4-dichlorobenzene would have a similar response and that the 1,2-dichlorobenzene response could be used to determine the concentration of 1,4-dichlorobenzene. Analyses of a liquid solution standard confirmed that the response factor for 1,4-dichlorobenzene was on average 3.2% less than that of 1,2-dichlorobenzene. A gas standard was prepared containing 1,2- and 1,4-dichlorobenzene at nominal concentrations of 250 nmol/mol (ppb). Analytical results showed that the concentration of 1,4-dichlorobenzene determined from 1,2-dichlorobenzene was within 3% of the gravimetric value. Further research using two standards containing 1,4-dichlorobenzene revealed that they agreed exactly with the gravimetric concentrations. These results verified the ability to prepare accurate gas standards of 1,4-dichlorobenzene in gas cylinders.

Langmuir–Blodgett films of side-chain polysiloxanes: synthesis, characterisation and pyroelectric behaviour

Four aliphatic acid side-chain polymers have been synthesized and evaluated, based upon two different polysiloxane backbones, namely poly(methylsiloxane) and poly(methylsiloxane–dimethylsiloxane). A study of their behaviour at the water/air interface has shown that stable, fluid molecular films are formed that can be transferred as monolayers onto hydrophilic substrates. Their surface pressure–area isotherms indicate that bunching of the polysiloxane backbones may occur at relatively high surface pressures. The alternate layer deposition process has been used, in which the polysiloxane is co-deposited with a monomeric aliphatic amine (icosylamine). This ABABA⋯ sequential transfer has been monitored using the piezoelectric quartz crystal microgravimetric technique in which the alternate layer is assembled on top of a bulk quartz crystal, the oscillation frequency of which is measured precisely. The relationship between the frequency change and the number of transferred polysiloxane/monomer icosylamine bilayers is linear for the three materials that could be deposited, indicating that the deposition process is highly reproducible. The pyroelectric effect in these films has been studied. These data indicate that the level of activity is not simply related to the fraction of the silicon units along the backbones which are substituted with aliphatic acid chains. There is likely to be a trade-off between the density of acid/amine interactions and the free volume in which molecular tilting can occur.

Effects of cervical spinal cord stimulation in experimental ischaemic oedema

Cervical spinal cord stimulation (SCS) has been used in an animal model of acute ischaemic brain oedema. In anaesthetized rats a temporary carotid bilateral occlusion of 60 minutes was carried out, followed by a reperfusion period of 30 minutes before sacrifice. Two electrodes were placed in each side of the duramater at C2 level. SCS was started either 60 minutes before ischaemia or at the beginning of the reperfusion period. The parameters of stimulation were: pulse width 0.1 ms; frequency of 25 cps; intensity at one third of the threshold which produced motor responses. The specific gravity of the brain was measured at different areas using a microgravimetric technique in a bromobenzene-petroleum column. Our results indicate that: 1) cervical SCS reduces ischaemic cerebral oedema, 2) the effect is more prominent using stimulation during the reperfusion period, and 3) there were no differences in mortality rates or in the pathological study.

Oxidation protection for a variety of transition metals and copper via surface silicides formed with silane containing atmospheres

The reaction of SiH4/H2 mixtures with iron, cobalt, nickel, copper, chromium, molybdenum, and tungsten, at temperatures between 350 and 800 °C and 1 atm of total pressure, was studied. When the amount of water vapor in the gas mixture is carefully controlled, a metal silicide diffusion coating forms at the appropriate treatment temperature. Cu silicide coatings form at temperatures as low as 350 °C. Metal silicide coatings for Fe, Ni, Co, and Cr form at intermediate temperatures (500–700 °C), and higher temperatures (above 700 °C) are required for W and Mo. Composition and structure of the metal silicide coatings were determined by Auger depth profiling and x-ray diffraction. Kinetics of the surface reaction between SiH4 and the metal substrate as well as the behavior of these coatings in oxidizing environments at high temperatures were studied by a microgravimetric technique. The metal silicide coatings provide oxidation protection for Fe, Ni, and Cr in pure O2 up to 1000 °C, for W and Mo in air up to 900 °C, and for Cu exposed to air up to 700 °C.

Impaired capillary perfusion and brain edema following experimental subarachnoid hemorrhage: a morphometric study

To evaluate microcirculatory disturbance and cerebral edema associated with subarachnoid hemorrhage (SAH), both stereological morphometry on the intraparenchymal capillary network and microgravimetry were performed on a rabbit SAH model. Autologous arterial blood (5 ml) was injected into the cisterna magna, and the animals were sacrificed at intervals of 6 hours, 1 day, 2 days, or 6 days after SAH. Capillaries in the piriform cortex, parasagittal cortex, and ventral brain stem of the midline-hemisectioned brain were injected with Evans blue dye 1 minute before sacrifice, and were planimetrically evaluated under a fluorescence microscope connected to an image analysis system. Stereological and morphological parameters including the volume density, surface density, numerical density, minimum intercapillary distance, and the diameter of Evans blue-perfused capillaries were also computed. In the piriform cortex and ventral brain stem, the volume and surface densities were significantly reduced and the minimum intercapillary distance was significantly increased 1 to 2 days after SAH. In the parasagittal cortex far from the cisternal clot, changes in the parameters were minimal. Cerebral blood volume (CBV) in the normal condition and edema formation associated with SAH were studied by the microgravimetric technique. The mean CBV in the parasagittal cortex, piriform cortex, and brain stem was 6.9%, 6.8%, and 5.6%, respectively. Following SAH, specific gravity in the piriform cortex and the ventral brain stem of the other side of the hemisectioned brain was significantly decreased at 1 to 2 days, showing a change parallel to that of the stereological parameters. The results obtained from the morphometric technique indicated the occurrence of impaired capillary perfusion and reduced capillary blood volume following SAH, while microgravimetry suggested the formation of brain edema during this period. These changes in the intraparenchymal vessels may play an important role in the pathophysiology of SAH.

Si diffusion coating on steels by SiH4/H2 treatment for high temperature oxidation protection

The reaction of SiH4/H2 mixtures with iron and steels was studied at a total pressure of 1 atm and temperatures above 500 °C. When the amount of water vapor in the gas mixture is carefully controlled, a metal silicide diffusion coating forms at low temperatures (below 900°C). Composition and structure of the Si diffusion coatings were determined with Auger depth profiling and x-ray diffraction. Kinetics of the surface reaction between SiH4, and the metal substrate as well as the behavior of these films in severe environments at high temperatures were studied by a microgravimetric technique. Characterization of these Si coatings on iron, low carbon steel (1010), 9% Cr/1% Mo steel (alloy A182F9), and stainless steels (310) and their applications to reduce oxidation, nitriding, or coking at high temperatures or corrosion in mineral acids are described.

Variations in rat mesenteric tissue thickness due to microvasculature.

Studies of microvascular, tissue and lymphatic transport using microphotometric and microfluorometric techniques are potentially subject to artifact due to variations in tissue specimen thickness. Absorbance techniques utilize the Lambert-Beer law in which A = log I0/I = act, where A is absorbance, I0 is incident light intensity, I is transmitted intensity, a is an absorbance coefficient, c is concentration of substance, and t is path length. If differences in t are known to be present, then inferences of changes in c from changes in A become suspect. In microfluorometry the amount of light gathered is proportional to the number of fluorochromes in the effective cuvette, which is determined by the microscope's numerical aperture and the sample thickness. If variations in thickness are known to occur, the effective cuvette volume may be changing; therefore, inferences of changes in fluorochrome concentration from changes in intensity become suspect. Existing data suggest that rat mesentery is 15-30 microns thick, but variation over a tissue region is unknown. Our goals are to determine thickness variation in avascular, fat-free mesenteric tissue regions; thickness variation near blood vessels; and average tissue thickness. Sprague-Dawley rats were anesthetized with Inactin. Mesenteric tissue from a loop of small intestine was draped over a platform for observation; thickness was measured with an oblique microscope and a microgravimetric technique. The average variation in avascular fat-free tissue was 1.1 micron/100-microns distance, and average thickness was 17.4 microns. There was a significant increase in thickness over the microvasculature.

Formation of oedema in transected rat sciatic nerve. A microgravimetric study.

The formation of oedema in peripheral nerves was studied in rats at intervals varying from 6 h to 14 days after transection of the right sciatic nerve. Samples were removed proximal and distal to the injury, and the degree of oedema was determined by a microgravimetric method and by measurements of the water content and of the fascicular area. Distal to the lesion, decreased density values indicating the presence of oedema were observed in samples examined after a survival period of 6 h-14 days. The water content and fascicular area were both increased in samples taken 24 h after injury. Fourteen days postinjury the water content had increased further. Proximal to the lesion, the water content and the fascicular area were increased in samples examined after a survival period of 24 h. Fourteen days after the injury, the increase in water content was even more pronounced. No changes were detected with the microgravimetric technique 6 and 24 h after the injury. Unexpectedly, animals surviving 14 days showed increased density values. The microgravimetric technique used is a valuable adjunctive method for quantitation of peripheral nerve oedema in the acute phase after a traumatic nerve injury. Later on, loss of axons and of myelin components, together with regenerative phenomena, influence the density values obtained. Quantitative methods for studying chronic peripheral nerve oedema should, therefore, be supplemented with other techniques.

Recirculation model following MCA occlusion in rats. Cerebral blood flow, cerebrovascular permeability, and brain edema.

A new model for establishing a successful and consistent arterial recirculation has been devised following middle cerebral artery (MCA) occlusion in the rat. A snare ligature was introduced at the stem of the MCA just distal to the lenticulostriate branches, and occlusion and recirculation were performed by pulling and releasing the thread. This method had an advantage over the use of a small clip which caused damage to the artery without good recirculation. Study of local cerebral blood flow using carbon-14 (14C)-iodoantipyrine, of cerebrovascular permeability using 14C-aminoisobutyric acid, and of brain-water content using the microgravimetric technique was performed upon recirculation following various periods of occlusion and compared with the results in permanent ischemia. A reactive hyperemia was noted within the previously ischemic area immediately upon recirculation following either a 30-minute or a 2-hour ischemic period. One or 2 hours later, delayed hypoperfusion developed in this region, but the circulation over the periphery of the ischemic area recovered well. Cerebrovascular permeability was not, however, altered during the time courses studied. Topographic changes in tissue specific gravity were compared between permanent and transient ischemia in the corresponding time-courses. Although there was a greater decrease in tissue specific gravity following recirculation when the ischemic period was maintained longer, edema formation was resolved by recirculation. Further study is required to determine thresholds of ischemic brain damage and edema formation at recirculation following focal cerebral ischemia.

Galactose neuropathy: impact of chronic endoneurial edema on nerve blood flow.

Peripheral neuropathy induced by galactose feeding results in endoneurial edema with increased tissue pressure and ultimate demyelination of nerve fibers. To assess the role of ischemia in the pathogenesis of this neuropathy, nerve blood flow was measured 6 months after the start of galactose ingestion, between the onset of edema and nerve fiber changes. Measurement was carried out by a noninvasive technique involving the use of [14C]iodoantipyrine as a radioactive tracer of tissue perfusion. A significant decline in nerve blood flow was found, which correlated positively with increased nerve water content as quantified by a microgravimetric technique. We sought to establish the pathogenic role of nerve edema in the development of schwannopathy and demyelination by morphological examination. It was found that Schwann cells appeared normal in areas of the peripheral nervous system in which edema does not occur, such as spinal ganglia and roots, whereas in regions in which there was edema, massive glycogen accumulation in Schwann cells and demyelination occurred. These findings suggest that edema, rather than hyperactivity in the sorbitol pathway, is responsible for the pathological changes in galactosemic neuropathy and that ischemia resulting from edema and increased endoneurial fluid pressure is the mechanism responsible for fiber injury.