Laryngopharyngeal reflux disease in singers: Pathophysiology, clinical findings and perspectives of a new patient-reported outcome instrument.

PURPOSE OF REVIEW: Laryngopharyngeal reflux (LPR) is an inflammatory disease associated with the development of voice disorder and vocal fold lesions. The occurrence of LPR in professional voice users as singers can have a dramatic impact of daily life. The aims of this paper is to review the current literature about the pathophysiological mechanisms underlying the development of voice disorder, especially in singers, and to propose a new patient-reported outcome instrument to assess complaints of these patients. RECENT FINDINGS: Many clinical and experimental studies reported that LPR leads to the development of significant macroscopic and microscopic histological changes in the mucosa of the vibratory margin of the vocal folds. Epithelial cell dehiscence, microtraumas, Reinke's space modifications, inflammatory infiltrates, mucosal drying, and epithelial thickening are associated with LPR. These histological changes may modify the biomechanical properties of the vocal fold tissue leading to hoarseness. In practice, singers with LPR may have normal or discretely pathological speaking voice but impaired singing voice (vocal fatigue, hoarseness, and loss of range). To date, the literature about the specific LPR signs and symptoms in singers is almost non-existent. However, singers are at high risk to present LPR because of necessary air support involving higher intra-abdominal pressure, increased stress due to career management and uncomfortable schedules, late meals just before sleep, bad nutrition habits like increased intake of citrus products, fats foods and spicy foods. PERSPECTIVES: The lack of clinical singer-reported outcome instrument may decrease the management of LPR in singers. In this context, the LPR Study Group of Young-Otolaryngologists of the International Federations of Oto-Rhino-Laryngological Societies (YO-IFOS) developed a new instrument to precisely assess symptoms related to LPR in singing voice. This instrument will be validated and could be used in clinical practice in voice centers.

Long-term Results of 18 Fat Injections in Unilateral Vocal Fold Paralysis.

OBJECTIVE: The purposes of this study were to assess the long-term efficacy of medialization laryngoplasty via injection of autologous fat in patients with unilateral laryngeal paralysis, and to discuss the results based on the volume of fat injected and the size of the initial glottic gap. STUDY DESIGN: This was a retrospective study with clinical reevaluation of 18 patients treated for unilateral laryngeal paralysis at Liège University Hospital between April 1, 2011, and December 1, 2014. METHOD: The voice examination included subjective scales (GRBAS and the Voice Handicap Index), a report on acoustic and aerodynamic voice parameters, and laryngostroboscopic assessment of glottic closure and mucosal wave (T0: preoperative; T1: immediate postoperative; T2: >1 year). RESULTS: The median follow-up duration was 19 months. We observed a significant improvement in maximum phonation time; mean flow rate; jitter; the Voice Handicap Index; the G, R, B, and A subscales of the GRBAS-I; and glottic closure at T1. These parameters remained stable over time, without any significant difference except for shimmer and glottic closure between T1 and T2. Regardless of the volume of fat injected and the magnitude of the initial glottic gap, we did not see any significant difference from one assessment time to another. CONCLUSION: Medialization laryngoplasty by means of the injection of autologous fat is a safe, effective surgical technique for patients with unilateral laryngeal paralysis regardless of the size of the initial glottic gap. The results are maintained longer than 1 year, and no evidence of significant resorption of the fat was found in our study over a period of 12-58 months. The volume of fat injected does not seem to affect the functional results.

[Laryngeal involvements in systemic diseases : a discussion based on a case report.] / Manifestations laryngées des maladies de système : cas clinique.

Systemic diseases can affect the larynx. The most common laryngeal involvements, although often unknown, consist in inflammatory laryngitis, laryngeal ulcers, cricoarytenoid arthritis, recurrent laryngeal nerve paresis and subglottic stenosis. The clinical case we report is more uncommon, but representative of autoimmune diseases : vocal folds bamboo nodes in a young female patient, age 34, suffering from active rheumatoid arthritis. In the present article, we detail the current knowledge of this pathology and later discuss different laryngeal involvements of systemic diseases by lesion type et their management.

Les maladies de système peuvent affecter le larynx. Leurs manifestations laryngées les plus fréquentes, bien qu'elles soient souvent méconnues, sont les laryngites inflammatoires, les ulcères laryngés, les arthrites crico-aryténoïdiennes, les parésies récurrentielles et les sténoses sousglottiques. Le cas clinique que nous rapportons ici est plus rare, mais caractéristique des maladies auto-immunes : des noeuds de bambou des cordes vocales chez une jeune patiente de 34 ans souffrant d'une polyarthrite rhumatoïde. Dans cet article, nous détaillons les connaissances actuelles sur cette pathologie et discutons ensuite les différentes manifestations laryngées des maladies de système par type de lésion et leur prise en charge.

MRI-based aortic blood flow model in 3D ballistocardiography.

Ballistocardiography (BCG) is a non-invasive technique which measures the acceleration of a body induced by cardiovascular activity, namely the force exerted by the beating heart. A one dimensional aortic flow model based on the transmission lines theory is developped and applied to the simulation of three dimensional BCG. A four-element Windkessel model is used to generate the pressure-wave. Using transverse MRI slices of a human subject, a reconstruction of the aorta allows the extraction of parameters used to relate the local change in mass of the 1D flow model to 3D acceleration BCG. Simulated BCG curves are then compared qualitatively with the ensemble average curves of the same subject recorded in sustained microgravity. Confirming previous studies, the main features of the y-axis are well simulated. The simulated z-axis, never attempted before, shows important similarities. The simulated x-axis is less faithful and suggests the presence of reflections.

Evaluation of ensemble averaging methods in 3D ballistocardiography.

Ballistocardiography (BCG) is a non-invasive technique which measures the acceleration of a body induced by cardiovascular activity, namely the force exerted by the beating heart. Measuring a BCG in a gravity-free environment provides ideal conditions where the subject is completely decoupled from its environment. Furthermore, because gravity constrains the motion in two dimensions, the non-negligible accelerations taking place in the third dimension are lost. In every experimental situation, the measured BCG signal contains artifacts pertaining to different causes. One of them is the undesirable involuntary movements of the subject. Ensemble averaging (EA) tackles the issue of constructing a typical one cardiac cycle BCG signal which best represents a longer recording. The present work compares state-of-the-art EA methods and proposes two novel techniques, one taking into account the ECG sub-intervals and the other one based on Dynamic Time Warping. The effects of lung volume are also assessed.

Three dimensional Ballistocardiogram and Seismocardiogram: what do they have in common?

3D-body accelerations, i.e. Ballistocardiograms (BCG) and Seismocardiograms (SCG), ECG and Impedance-cardiograms (ICG) were recorded on healthy volunteers participating to the European Space Agency (ESA) 59th parabolic flight campaign. In the present paper we document the similarities and differences that can be seen in the seismo- and ballisto-cardiogram signals in different positions (standing and supine) under normal gravity condition as well as during the weightlessness phases (0G) of a parabolic flight. Our results demonstrate that SCG and BCG both present a similar three dimensional (3D) nature, with components of the BCG having lower frequency content than the SCG. The recordings performed in the 0G environment are the one with the smoothest shape and largest maximum magnitude of the Force vector. The differences seen between SCG and BCG stress further the importance for the need of using different nomenclature for the identification of peaks in both signals.

Estimating the center of mass of a free-floating body in microgravity.

This paper addresses the issue of estimating the position of the center of mass (CoM) of a free-floating object of unknown mass distribution in microgravity using a stereoscopic imaging system. The method presented here is applied to an object of known mass distribution for validation purposes. In the context of a study of 3-dimensional ballistocardiography in microgravity, and the elaboration of a physical model of the cardiovascular adaptation to weightlessness, the hypothesis that the fluid shift towards the head of astronauts induces a significant shift of their CoM needs to be tested. The experiments were conducted during the 57th parabolic flight campaign of the European Space Agency (ESA). At the beginning of the microgravity phase, the object was given an initial translational and rotational velocity. A 3D point cloud corresponding to the object was then generated, to which a motion-based method inspired by rigid body physics was applied. Through simulations, the effects of the centroid-to-CoM distance and the number of frames of the sequence are investigated. In experimental conditions, considering the important residual accelerations of the airplane during the microgravity phases, CoM estimation errors (16 to 76 mm) were consistent with simulations. Overall, our results suggest that the method has a good potential for its later generalization to a free-floating human body in a weightless environment.

Realistic analytical phantoms for parallel magnetic resonance imaging.

The quantitative validation of reconstruction algorithms requires reliable data. Rasterized simulations are popular but they are tainted by an aliasing component that impacts the assessment of the performance of reconstruction. We introduce analytical simulation tools that are suited to parallel magnetic resonance imaging and allow one to build realistic phantoms. The proposed phantoms are composed of ellipses and regions with piecewise-polynomial boundaries, including spline contours, Bézier contours, and polygons. In addition, they take the channel sensitivity into account, for which we investigate two possible models. Our analytical formulations provide well-defined data in both the spatial and k-space domains. Our main contribution is the closed-form determination of the Fourier transforms that are involved. Experiments validate the proposed implementation. In a typical parallel magnetic resonance imaging reconstruction experiment, we quantify the bias in the overly optimistic results obtained with rasterized simulations-the inverse-crime situation. We provide a package that implements the different simulations and provide tools to guide the design of realistic phantoms.

[Comparative study of cyclopentolate drops versus spray in cycloplegia in children]. / Etude comparative de la cycloplégie par cyclopentolate en gouttes et en spray chez des enfants.

INTRODUCTION: Instillation of cyclopentolate drops with their irritant effect is difficult for children to bear. The purpose of this study was to compare the tolerance and efficacy of cyclopentolate spray versus drops. MATERIAL AND METHODS: The cycloplegic effect of cyclopentolate spray prepared and conditioned in the hospital was compared with drops in 62 eyes of 32 children consulting in our department. The nonparametric Wilcoxon test for paired data was used to assume there was no significant difference between the refractive measurements with spray or drops. RESULTS: The mean age of our patients was 6.3 years (SD, 3.4 years). The refractive values ranged from -17.3 diopters to +8 spheric diopters and -4 to 0 cylindric diopters. The nonparametric Wilcoxon test for paired data showed no significant difference between cycloplegic measurements with drops or spray. CONCLUSION: Cyclopentolate spray is a good alternative to traditional drops, leading to equal cycloplegic efficacy but greater tolerance in children and easier administration by the nursing staff.

Neurosedation in dentistry of the disabled patient: the use of midazolam, propofol, and remifentanil.

AIM: This prospective randomized study, deals with neurosedation in dental treatment of 200 disabled patients and unable to cooperate, subdivided in 4 groups of 50 male only patients, with age ranging from 28 to 59 (39+/-11), ASA I-III. METHODS: The pharmaceuticals used were Midazolam (group MID) Propofol (group Prop) and Remifentanil. Midazolam and Propofol were used following a bolus-infusion sequence, both separately and in combination among themselves (MID\PROP group), or with an opioid, Remifentanil (MID\PROP\REMI group). ECG, heart rate , non invasive blood pressure (NIBP), SaO(2), EtCO(2) during the procedure were monitored. Induction time, duration of the sedation, recovery time and discharge were reported. RESULTS: The statistical analysis demonstrated the superiority of the PROP group for induction time in minute (3.1+/-0.5) in comparison with the MID group (10.6+/-2.1), the MID\PROP group (4.3+/-1.3) and MID\PROP\REMI (3.7+/-1.2). The recovery and discharge times have confirmed the superiority of the MID\PROP\REMI group in comparison with the other 3 groups. CONCLUSION: This combination proved best at leveraging the synergistic characteristics of each single pharmaceutical and minimizing the collateral effects of each individually.

Postnatal bone marrow stromal cells elicit a potent VEGF-dependent neoangiogenic response in vivo.

Bone marrow stromal cells (MSCs) are pluripotent cells capable of differentiation into several tissue types. This present study was performed to determine their functional neoangiogenic potential in vivo. Whole bone marrow was harvested from C57Bl/6 mice, and the adherent cellular fraction was culture expanded for 14 doublings. These MSCs were resuspended in Matrigel and their angiogenic effect assessed in isogenic recipients. At 2 weeks postimplantation, the mean vascular density in Matrigel plugs containing 2 x 10(6) MSCs/ml was 41+/-5.0 blood vessels (BVs)/mm(2) compared to 0.5+/-0.7 for empty Matrigel (P<0.001). In comparison, Matrigel plugs containing either recombinant murine VEGF 165 at 50 ng/ml or bovine bFGF at 1000 ng/ml generated 21+/-5 and 11+/-2.0 BV/mm(2), respectively. Arteriogenesis was observed only in the MSC-containing implants. With the use of LacZ retroviral labeling of ex vivo expanded MSCs, we show that approximately 10% of LacZ(+)MSCs differentiated into CD31(+) and VEGF(+) endothelial cells. More than 99% of the neoangiogenic phenomena arose from recruitment of host-derived LacZ(null) vascular structures. Neutralizing anti-VEGF antibodies inhibited the MSC-initiated angiogenic response in vivo by 85% (P<0.001). In conclusion, MSCs have the ability to effectively recruit and participate in angiogenesis and arteriogenesis de novo and VEGF plays a central role in the observed host-derived angiogenic response. We propose that ex vivo expanded autologous MSCs may serve as cell therapy to promote therapeutic angiogenesis.

Preservation of graft-versus-infection effects after suicide gene therapy for prevention of graft-versus-host disease.

The main complications following allogeneic hematopoietic stem cell transplantation are graft-versus-host disease and poor immune reconstitution leading to severe infections. Mature donor T cells present in the transplant facilitate T cell reconstitution in adults, but also induce graft-versus-host disease, which itself impairs immune reconstitution. Thus, infusing a large number of donor T cells with a diverse repertoire should accelerate functional immune reconstitution after transplantation, only if graft-versus-host disease can be controlled. We previously demonstrated that preventive treatment with ganciclovir could control graft-versus-host disease in mice if donor T cells are made to express viral thymidine kinase as a "suicide" gene. Here we evaluated the recovery of functional antiviral immune responses in such mice. Irradiated mice received an allogeneic hematopoietic stem cell transplantation with thymidine kinase-expressing T cells and were protected from graft-versus-host disease by ganciclovir treatment, and then challenged with lymphocytic choriomeningitis virus. Grafted mice could mount efficient antilymphocytic choriomeningitis virus immune responses leading to viral elimination. Furthermore, when transplanted cells were obtained from mice previously immunized against lymphocytic choriomeningitis virus, grafted mice developed memory-type accelerated responses against the virus. We conclude that efficient graft-versus-infection effects can be mediated by naive T cells and memory donor T cells that persist after suicide gene therapy for prevention of graft-versus-host disease.

Immunological defects after suicide gene therapy of experimental graft-versus-host disease.

Donor T cells are beneficial for engraftment, immune reconstitution, and antileukemic effects after allogeneic marrow transplantation, but they also cause graft-versus-host disease. Treatment with ganciclovir can control graft-versus-host disease if donor T cells are genetically engineered to express viral thymidine kinase. Clinical protocols with thymidine kinase-expressing T cells currently prescribe the curative use of ganciclovir for genetic immunosuppression only after clinical manifestations of graft-versus-host disease have appeared. The aim of this work was to compare early/preventive versus delayed/curative treatment of GVHD. Here, we found that ganciclovir administered early after experimental marrow transplantation was highly effective in preventing graft-versus-host disease caused by thymidine kinase-expressing T cells, and surviving recipient mice were able to mount a T cell-dependent B cell response. In contrast, curative ganciclovir administration later after transplantation was much less effective in treating graft-versus-host disease and surviving recipients had markedly impaired immune function. These findings should be considered in the development of future clinical trials using thymidine kinase-expressing T cells; to date, such trials have envisaged the use of GCV to treat only declared graft-versus-host disease. The use of thymidine kinase-expressing T cells for conditional elimination of activated T cells after allogeneic marrow transplantation offers a promising new approach for the control of graft-versus-host disease. The versatility of the thymidine kinase/ganciclovir system offers clinical options depending on whether thymidine kinase-expressing T cells are infused at the time of bone marrow transplantation or in a delayed manner, and depending on whether GCV is administered in an early/preventive or delayed/curative manner. The rationale underlying these options is more complex than it may appear and is likely to have a profound impact on the efficacy of such treatments. In the present work, we analyze the immunological impact when GCV is administered in an early/preventive or delayed/curative manner. Our results demonstrate that the delayed/curative strategy is clearly associated with severe immunological defects. To our knowledge, this is the first report of immunodeficiency subsequent to suicide gene therapy for GVHD.

PEG-Hemoglobin as a resuscitation solution in the treatment of hypovolemic shock in the anesthetized rat.

This study was designed to determine the advantages of using the hemoglobin-based oxygen carrier, polyethylene glycol conjugated bovine hemoglobin (PEG-Hb), as an additive to Ringer's lactate solution (RLS) for the treatment of acute hemorrhage in anesthetized female rats. Different compositions of PEG-Hb and RLS were administered intravenously in a paradigm that provided 30 ml/kg of resuscitation fluid following an episode of 15 min of hypotension. Hypotension was achieved by the removal of blood (1 ml/min) from the femoral vein until the mean arterial pressure was lowered to or below 50 mmHg and subsequently maintained until resuscitation. Short-term cardiovascular assessment showed that resuscitation fluids containing PEG-Hb resulted in higher mean arterial pressure, aortic blood flow, renal blood flow, and less dramatic shifts in arterial base excess and respiratory blood gases than plain RLS. The long-term survival experiment showed lower lactate dehydrogenase, alkaline phosphatase, and serum glutamic pyruvic transaminase levels in most groups resuscitated with solutions containing PEG-Hb, but no differences in survival (100%) were observed. The data suggest that the addition of PEG-Hb to RLS improves its resuscitative effects. Specifically, a solution of 50% RLS:50% PEG-Hb appeared to have the most favorable cardiovascular and metabolic effects in this anesthetized rat hypovolemic shock resuscitation model. Presumably, the improved effects seen with the addition of PEG-Hb were due to its innate plasma expansion and oxygen-delivery capabilities.

Fertile homozygous transgenic mice expressing a functional truncated herpes simplex thymidine kinase delta TK gene.

Dividing cells expressing the Herpes simplex type 1 thymidine kinase (TK) can be killed upon ganciclovir treatment. Likewise, conditional cell knock-out can be obtained in transgenic mice expressing a TK gene placed under the control of tissue-specific regulatory sequences. Such animals provide powerful experimental systems for assessing the functional role of specific cell populations through their time-controlled ablation. However, whatever the regulatory sequences used, a leaky toxic overexpression of TK in testis renders male TK-transgenic mice sterile and prevents the generation of homozygous TK-expressing animals. To solve this problem, we designed a truncated TK variant (delta TK) not expressed in the testis. We generated transgenic mice expressing delta TK under the control of lymphocyte-specific regulatory sequences derived from the CD4 gene. The delta TK protein expressed in T-lymphocytes allowed the conditional ablation of activated T-cells in vitro and in vivo. Importantly, for one transgenic line we could generate fertile homozygous mice harboring a functional delta TK transgene. delta TK should thus dramatically facilitate the development of transgenic mice expressing a conditional suicide gene.

Evaluation of the oxygen delivery ability of PEG-hemoglobin in Sprague-Dawley rats during hemodilution.

Polyethylene glycol (PEG) conjugation allows bovine hemoglobin (Hb) to retain its oxygen delivery capability while increasing its plasma expansion capacity. To determine whether PEG-Hb's ability to sustain life is due to its oxygen delivery capability rather than its plasma expansion capacity, Sprague-Dawley rats were exchange-transfused up to an 85% hematocrit reduction with either PEG-Hb, PEG-50%-methemoglobin (PEG-mHb), PEG-carbon monoxide hemoglobin (PEG-COHb) or PEG-human serum albumin (PEG-HSA). Survival and respiratory rates were monitored during the exchange transfusion, at five minutes, 24 hours and 48 hours post operative. Rats surviving 14 days were evaluated for hematology, blood chemistry and histopathology. Rats infused with PEG-Hb had a survival rate of 100% during the transfusion and 79% at 24 hours, as compared to 24 hour survival rates of 30% for PEG-mHb, and 0% for both PEG-COHb and PEG-HSA. PEG-Hb treated rats that survived the 2 week observation period had normal hematological and blood chemistry levels and no significant morphological effects. Therefore, this study demonstrates that PEG-Hb can sustain life while similar plasma expansion agents with less oxygen delivery capability are not as effective.

Position-dependent variegation of a CD4 minigene with targeted expression to mature CD4+ T cells.

The CD4 gene follows a complex and highly regulated pattern of expression throughout T cell development. This expression is governed by different regulatory elements that have been partly identified, including a promoter, a proximal enhancer, and a silencer. Here we show that a CD4 minigene comprising a combination of these elements is specifically expressed in mature CD4+ T cells of transgenic mice, but not in CD4+CD8+ double positive thymocytes. The proportion of transgene-expressing CD4+ T cells was constant within a given transgenic line, but varied greatly from one line to another. We demonstrate that this pattern of expression is due to integration of the transgene within or in the vicinity of centromeric heterochromatin. This position-effect variegation demonstrated with a short CD4 transgene has not been observed with larger ones containing additional regulatory sequences, suggesting that the CD4 gene contains a locus control region. Such position-dependent effects must be taken into consideration when developing transgenic models or gene transfer vectors because they can result in the absence of transgene expression in a subpopulation of target cells. Finally, the combination of the CD4 gene silencer, proximal enhancer, and promoter provides an interesting tool to selectively express genes of interest in mature CD4+ T cells of transgenic mice and for the development of gene therapy vectors.

Physiological effect of polyethylene glycol conjugation on stroma-free bovine hemoglobin in the conscious dog after partial exchange transfusion.

This study was designed to determine the effect of polyethylene glycol (PEG) conjugation on stroma-free bovine hemoglobin. This was accomplished by examining the effects of unmodified stroma-free bovine hemoglobin (bovine Hb), PEG modified bovine hemoglobin (PEG-Hb) and dextran 70 on heart rate (HR), mean arterial pressure (MAP), gross renal morphology, blood chemistry, and hemoglobinuria development in conscious beagle dogs following a 30% exchange transfusion. Dogs were implanted with telemetric blood pressure probes and after 2 weeks underwent an isovolumic 30% blood volume exchange transfusion. Dogs treated with bovine Hb displayed a significant increase in MAP for 2 h following the exchange transfusion with no effect on HR. These animals exhibited significant levels of hemoglobinuria (> 20% of infused dose) within 24 h. Histopathologically, all bovine Hb infused dogs displayed renal tubular vacuolization, with 2 dogs showing regions of tubular casts and tubular cell regeneration. PEG-Hb was shown to have a circulatory half-life of 58.3 +/- 2.4 h and caused no significant changes in MAP or HR throughout the study period. Dogs excreted less than 0.1% of infused PEG-Hb within 24 h and displayed only renal tubular epithelial cell vacuolization. Dextran 70 caused a slight but insignificant decrease in MAP, elevated the HR, and exhibited only slight renal vacuole formation. Blood chemistry remained essentially stable following exchange transfusion with all the test articles. The conjugation of PEG to hemoglobin greatly increased the parent protein's vascular retention while attenuating some of its less favorable attributes.

Transitional vacuole formation following a bolus infusion of PEG-hemoglobin in the rat.

This study was designed to assess the morphological effects of a bolus infusion of PEG-hemoglobin on the heart, lung, liver, spleen and kidney of laboratory rats. Of particular interest was the determination of PEG-hemoglobin's potential to form vacuoles in the tissues and whether these were transitory and article specific. One hundred ten female Sprague-Dawley rats were used in this study. The first experiment determined whether vacuole formation was test article specific by infusing either stroma-free bovine hemoglobin, PEG-hemoglobin, bovine serum albumin, PEG-bovine serum albumin or free PEG. The second experiment assessed the transitory nature of vacuolization. In both experiments, unconscious rats received an intravenous top-loading (bolus) injection of test article via the tail vein. Rats were sacrificed at various time points following administration and had their tissues examined for the presence of vacuoles by light microscope morphological examination and iron staining. Formation of vacuoles appeared to be test article specific with only prolonged circulating, high solute test articles producing vacuoles. These vacuoles appeared dose responsive and transitory in nature. The vacuolization found was non-toxic and believed to be due to the known effect of lysosomal overloading following the phagocytosis of vascularly persistent high solute test articles.

The effects of hemodilution with polyethylene glycol bovine hemoglobin (PEG-Hb) in a conscious porcine model.

BACKGROUND: Severe hemodilution in large mammals has been used rigorously for the safety and efficacy testing of hemoglobin-based red blood cell substitutes. The effects of hemodilution with polyethylene glycol-modified bovine hemoglobin (PEG-Hb) were investigated in an unanesthetized porcine model. METHODS: Immature Yorkshire cross barrow pigs were subjected to exchange transfusion with PEG-Hb (n = 6) or dextran 70 (n = 4) until an 80% reduction in hematocrit was achieved. RESULTS: All six (100%) PEG-Hb-infused pigs and only one (25%) dextran 70 control pig survived the resultant reduction in erythrocytes. Heart rates and mean arterial pressure were not significantly affected by PEG-Hb infusion. Pigs infused with PEG-Hb maintained normal levels of blood pH, PO2, and PCO2 while dextran 70 controls showed low PvO2, PaCO2, and the development of acidosis. Histological evaluation revealed that the surviving dextran 70 control animal exhibited possible anoxia-induced hepatic centrilobular necrosis. PEG-Hb-treated pigs demonstrated the presence of renal tubular cell cytoplasmic vacuoles and vacuolated macrophages in spleens. CONCLUSIONS: The results indicate that PEG-Hb effectively supports life close to lethal levels of anemia.