Synergy of a STING agonist and an IL-2 superkine in cancer immunotherapy against MHC I-deficient and MHC I+ tumors.

Cyclic dinucleotides (CDN) and Toll-like receptor (TLR) ligands mobilize antitumor responses by natural killer (NK) cells and T cells, potentially serving as complementary therapies to immune checkpoint therapy. In the clinic thus far, however, CDN therapy targeting stimulator of interferon genes (STING) protein has yielded mixed results, perhaps because it initiates responses potently but does not provide signals to sustain activation and proliferation of activated cytotoxic lymphocytes. To improve efficacy, we combined CDN with a half life-extended interleukin-2 (IL-2) superkine, H9-MSA (mouse serum albumin). CDN/H9-MSA therapy induced dramatic long-term remissions of the most difficult to treat major histocompatibility complex class I (MHC I)­deficient and MHC I+ tumor transplant models. H9-MSA combined with CpG oligonucleotide also induced potent responses. Mechanistically, tumor elimination required CD8 T cells and not NK cells in the case of MHC I+ tumors and NK cells but not CD8 T cells in the case of MHC-deficient tumors. Furthermore, combination therapy resulted in more prolonged and more intense NK cell activation, cytotoxicity, and expression of cytotoxic effector molecules in comparison with monotherapy. Remarkably, in a primary autochthonous sarcoma model that is refractory to PD-1 checkpoint therapy, the combination of CDN/H9-MSA with checkpoint therapy yielded long-term remissions in the majority of the animals, mediated by T cells and NK cells. This combination therapy has the potential to activate responses in tumors resistant to current therapies and prevent MHC I loss accompanying acquired resistance of tumors to checkpoint therapy.

The changing treatment landscape in haemophilia: from standard half-life clotting factor concentrates to gene editing.

Congenital haemophilia A (factor VIII deficiency) and B (factor IX deficiency) are X-linked bleeding disorders. Replacement therapy has been the cornerstone of the management of haemophilia, aiming to reduce the mortality and morbidity of chronic crippling arthropathy. Frequent intravenous injections are burdensome and costly for patients, consequently with poor adherence and restricted access to therapy for many patients worldwide. Bioengineered clotting factors with enhanced pharmacokinetic profiles can reduce the burden of treatment. However, replacement therapy is associated with a risk for inhibitor development that adversely affects bleeding prevention and outcomes. Novel molecules that are subcutaneously delivered provide effective prophylaxis in the presence or absence of inhibitors, either substituting for the procoagulant function of clotting factors (eg, emicizumab) or targeting the natural inhibitors of coagulation (ie, antithrombin, tissue factor pathway inhibitor, or activated protein C). The ultimate goal of haemophilia treatment would be a phenotypical cure achievable with gene therapy, currently under late phase clinical investigation.

Percutaneous albumin/doxycycline injection versus open surgery for aneurysmal bone cysts in the mobile spine.

PURPOSE: This study aimed to validate the safety and effectiveness of percutaneous doxycycline/albumin injection for spinal aneurysmal bone cysts (ABCs) as an alternative to open surgery. METHODS: From January 2000 to December 2016, 25 patients who had no/minor neurological deficits (modified Frankel scale D or E) and acceptable local stability (spinal instability neoplastic score < 12) were included in the study, of whom 14 were treated with percutaneous doxycycline/albumin injection (injection group) and 11 were treated with open surgery (surgery group). The demographic and clinical information of the injection and surgery groups were recorded and compared. RESULTS: In the injection group, lesion size was significantly reduced in all 14 patients, all patients showed complete neurological recovery, and 13 patients had complete relief of neck pain; their mean visual analogue scale (VAS) decreased from 3.4 to 0.5. No complication or recurrence was observed during the mean 30.7-month follow-up (range, 24-50 months). In the surgery group, 9 patients had complete neurological recovery and 2 patients had residual slight paresthesia; their mean VAS decreased from 3.4 to 0.5. Two had local recurrence during their follow-up at 66.5 months (range, 50-96 months). Compared with the surgery group, the injection group showed no significant difference in the rate of recurrence (P = 0.14) and complication (P = 0.36). CONCLUSIONS: Percutaneous doxycycline/albumin injection for spinal ABCs can be safely and effectively performed in well-selected cases. It could serve as an alternative treatment, especially for spinal ABCs lesions with acceptable local stability and in patients without severe neurological deficits. These slides can be retrieved under Electronic Supplementary Material.

The correlation between preoperative levels of albumin and tlc and mortality in patients with femoral neck fracture.

A femoral neck fracture in an elderly patient often represents a major challenge for the orthopaedic surgeon who has to face not only the fracture, but also all the multiple issues related to age. Among others, malnutrition has been recognised as an important factor associated with severe aggravation in these patients. One-hundred-and-forty-seven patients were enrolled to investigate the use of two markers of patient nutritional status, i.e. serum albumin level and total leukocyte count (TLC), as predictors of mortality in the elderly patient suffering from proximal femur fracture. We found that low preoperative values of serum albumin and TLC proved to be directly related to worse outcomes. Therefore, these exams can be useful to identify patients with a femoral neck fracture that have higher risk of malnutrition and consequent higher mortality and that can benefit from some measures, such as albumin or protein nutritional supplement.

Entering new areas in known fields: recombinant fusion protein linking recombinant factor VIIa with recombinant albumin (rVIIa-FP) - advancing the journey.

The novel fusion protein linking recombinant factor VIIa with recombinant albumin (rVIIa-FP) is designed to extend the half-life of recombinant factor VIIa (rFVIIa) and improve the care of hemophilia A or B patients with inhibitors. Preclinical studies in various animal models have demonstrated markedly improved pharmacokinetic and pharmacodynamic properties, as well as prolonged retention in the joint tissues, of rVIIa-FP compared with a commercially available rFVIIa (NovoSeven®). A phase I study in healthy volunteers - the first study in the PROLONG-7FP program - confirmed that rVIIa-FP has a good tolerability profile in doses of up to 1,000µg/kg and has demonstrated enhanced pharmacodynamic activity relative to rFVIIa. The half-life of rVIIa-FP at the highest dose investigated in the study was 8.5hours, which represents a 3- to 4-fold half-life extension compared with rFVIIa. Encouraging results from preclinical and phase I studies have led to the initiation of clinical studies of rVIIa-FP in patients with congenital hemophilia A or B and inhibitors, and in patients with confirmed factor VII deficiency. The results from these studies are awaited with interest by clinicians and patients alike.

The Coagulation Factor XIIa Inhibitor rHA-Infestin-4 Improves Outcome after Cerebral Ischemia/Reperfusion Injury in Rats.

BACKGROUND AND PURPOSE: Ischemic stroke provokes severe brain damage and remains a predominant disease in industrialized countries. The coagulation factor XII (FXII)-driven contact activation system plays a central, but not yet fully defined pathogenic role in stroke development. Here, we investigated the efficacy of the FXIIa inhibitor rHA-Infestin-4 in a rat model of ischemic stroke using both a prophylactic and a therapeutic approach. METHODS: For prophylactic treatment, animals were treated intravenously with 100 mg/kg rHA-Infestin-4 or an equal volume of saline 15 min prior to transient middle cerebral artery occlusion (tMCAO) of 90 min. For therapeutic treatment, 100 mg/kg rHA-Infestin-4, or an equal volume of saline, was administered directly after the start of reperfusion. At 24 h after tMCAO, rats were tested for neurological deficits and blood was drawn for coagulation assays. Finally, brains were removed and analyzed for infarct area and edema formation. RESULTS: Within prophylactic rHA-Infestin-4 treatment, infarct areas and brain edema formation were reduced accompanied by better neurological scores and survival compared to controls. Following therapeutic treatment, neurological outcome and survival were still improved although overall effects were less pronounced compared to prophylaxis. CONCLUSIONS: With regard to the central role of the FXII-driven contact activation system in ischemic stroke, inhibition of FXIIa may represent a new and promising treatment approach to prevent cerebral ischemia/reperfusion injury.

Eculizumab en recién nacido con síndrome hemolitico urémico atípico: a propósito de un caso / Eculizumab for atypical hemolytic uremic syndrome in newborn: a case report

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Neuroprotection for ischaemic stroke: translation from the bench to the bedside.

Neuroprotection seeks to restrict injury to the brain parenchyma following an ischaemic insult by preventing salvageable neurons from dying. The concept of neuroprotection has shown promise in experimental studies, but has failed to translate into clinical success. Many reasons exist for this including the heterogeneity of human stroke and the lack of methodological agreement between preclinical and clinical studies. Even with the proposed Stroke Therapy Academic Industry Roundtable criteria for preclinical development of neuroprotective agents for stroke, we have still seen limited success in the clinic, an example being NXY-059, which fulfilled nearly all the Stroke Therapy Academic Industry Roundtable criteria. There are currently a number of ongoing trials for neuroprotective strategies including hypothermia and albumin, but the outcome of these approaches remains to be seen. Combination therapies with thrombolysis also need to be fully investigated, as restoration of oxygen and glucose will always be the best therapy to protect against cell death from stroke. There are also a number of promising neuroprotectants in preclinical development including haematopoietic growth factors, and inhibitors of the nicotinamide adenine dinucleotide phosphate oxidases, a source of free radical production which is a key step in the pathophysiology of acute ischaemic stroke. For these neuroprotectants to succeed, essential quality standards need to be adhered to; however, these must remain realistic as the evidence that standardization of procedures improves translational success remains absent for stroke.

Lipotoxicidade na leptospirose humana: aspectos prognósticos e potencial efeito benéfico da administração de albumina / Lipotoxicity in human leptospirosis: prognostics aspects and potential beneficial effect of albumin administration

A leptospirose humana é uma doença infecciosa aguda de amplo espectro clínico e que cursa com alterações metabólicas e dislipidêmicas envolvendo colesterol total e frações, triglicerídeos e ácidos graxos não esterificados (AGNEs). Dentre os mecanismos celulares envolvidos na sua fisiopatologia encontram-se a inibição da enzima Na, K ATPase pela endotoxina GLP e a lipotoxicidade, ambos agravados pela redução dos níveis circulantes da albumina, molécula que exerce um papel fundamental na adsorção de moléculas lipídicas. Neste estudo observacional, determinamos as concentrações séricas de bilirrubina, creatinina e albumina e, pela técnica de cromatografia líquida de alta performance, a concentração sérica dos AGNEs de cadeia longa (C16: C18) de 27 pacientes com síndrome de Weil durante o período de internação hospitalar, dos quais cinco vieram a falecer. Verificamos correlações significantes (p<0,05) ao longo da internação hospitalar, nas concentrações séricas de marcadores bioquímicos de gravidade da doença (bilirrubina, creatinina e albumina), AGNEs, ácido oléico e ácido linoléico, e relação molar ácido oléico/albumina, com r (Pearson) de -0,7981, -0,7699, 0,9014, -0,8795 -0,9816, -0,9694, -0,9821, respectivamente. A relação molar ácido oléico/albumina e ácido oléico+linoléico/albumina foi significantemente mais elevada nos pacientes que faleceram (p<0,001), retornando aos valores semelhantes aos do grupo controle nos pacientes que evoluíram para a cura. Na análise por Curva Roc, a relação molar ácido oléico/albumina se mostrou um bom teste preditivo, com valor de corte 0,705 associado com maior especificidade e sensibilidade prognóstica. Nossos resultados sugerem que a utilização parenteral da albumina humana em pacientes com leptospirose pode ser uma potente ferramenta terapêutica nos casos mais graves ao interferir positivamente no resgate do equilíbrio bioquímico das relações molares ácido oléico/algumina e ácido oléico+linoléico/algumina.

Human leptospirosis is an acute infectious disease with a broad clinical spectrum. It courses with metabolic and dyslipidemic alterations, involving total cholesterol and fractions, triglycerides and nonesterified fatty acids (NEFAs). The cellular mechanisms involved in its pathogenesis include the inhibition of the enzyme sodium-potassium adenosine triphosphatase and lipotoxicity. Both mechanisms are aggravated by the reduction of serum levels of albumin, a molecule that plays a fundamental role in the absorption of lipid molecules. In this observational study, we determined the serum concentrations of bilirubin, creatinine and albumin, and, by High Performance Liquid Chromatography, the serum concentrations of long chain NEFAs (C16: C18) during the period of hospitalization of 27 patients with Weil's syndrome, five of whom progressed to death. Significant correlations were found between the length of hospitalization and serum concentrations of biochemical markers of severity (bilirubin, creatinine, albumin), NEFAs, oleic acid and linoleic acid, and the oleic acid: albumin molar ratio, with r (Pearson) of de -0,7981, -0,7699, 0,09014, -0,8795 -0,9816, -0,9694, -09821 respectively. The oleic acid: albumin molar ratio and oleic-plus-linoleic acid: albumin molar ratio were significantly higher in the patients who progressed to death, whereas in the cured patients this ratio decreased to levels that were similar to those found in the control group. Roc Curve analysis for the acid oleic: albumin molar ratio proved a good predictive test, with value of cutting 0.705 associated with greater specificity and prognostic sensitivity. Our results suggest that parenteral administration of human albumine may interfere positively in the rescue of biochemical balance of oleic acid: albumin molar ratio and oleic-plus-linoleic acid: albumin molar ratio and be a therapeutic tool for severe cases of leptospirosis.

Malnutrition and inflammation in acute kidney injury due to earthquake-related crush syndrome.

BACKGROUND: Malnutrition and inflammation are common and serious complications in patients with acute kidney injury (AKI). However, the profile of these complications in patients with AKI caused by crush syndrome (CS) remains unclear. This study describes the clinical characteristics of malnutrition and inflammation in patients with AKI and CS due to the Wenchuan earthquake. METHODS: One thousand and twelve victims and eighteen healthy adults were recruited to the study. They were divided into five groups: Group A was composed of victims without CS and AKI (904 cases); Group B was composed of patients with CS and AKI who haven't received renal replacement therapy (RRT) (57 cases); and Group C was composed of patients with CS and AKI receiving RRT (25 cases); Group D was composed of earthquake victims with AKI but without CS (26 cases); and Group E was composed of 18 healthy adult controls. The C-reactive protein (CRP), prealbumin, transferrin, interleukin-6 and TNF-alpha were measured and compared between Group E and 18 patients from Group C. RESULTS: The results indicate that participants in Group C had the highest level of serum creatinine, blood urea nitrogen and uric acid. Approximately 92% of patients with CS who had RRT were suffering from hypoalbuminemia. The interleukin-6 and CRP levels were significantly higher in patients with CS AKI receiving RRT than in the control group. Patients in Group C received the highest dosages of albumin, plasma or red blood cell transfusions. One patient in Group C died during treatment. CONCLUSIONS: Malnutrition and inflammation was common in patients with earthquake-related CS and had a negative impact on the prognosis of these subjects. The results of this study indicate that the use of RRT, intensive nutritional supplementation and transfusion alleviated the degree of malnutrition and inflammation in hemodialysis patients with crush syndrome.

Induced plasma expander-like properties as a function of PEG-chains on extension arm facilitated PEGylation of albumin: "mushroom to brush-like" conformational transition of the PEG-albumin conjugate.

Plasma expander-like properties of albumin induced on hexa as well as dodecacPEGylation using Extension Arm Facilitated PEGylation platform make it an excellent resuscitation fluid. PEGylation induced changes in the structure, drug binding, and plasma expander-like properties of bovine serum albumin has been now investigated as a function of PEGylation. The molecular volume of albumin increases on PEGylation nearly linearly; in the beginning up to about six PEG chains are conjugated, then plateau off, while the viscosity and colloidal osmotic pressure change very little initially and then increase exponentially as a function of PEG chains conjugated. PEGylation has essentially no influence on the secondary structure or drug properties of albumin. Tryphtophyl fluorescence of albumin is quenched on PEGylation as a direct correlate of the changes in molecular radius of PEG-albumin. It is concluded that hexaPEGylated and dodecaPEGylated albumin belong to two different configurational states of PEG-albumin in terms of packing of PEG-chains on the molecular surface of the protein. The results suggest a transition of PEGylated albumin from the initial mushroom-like conformation to brush conformation as the PEGylation increases. The therapeutic efficacy of the two PEGylated species is needed to establish the optimum level of PEGylation to function as resuscitation fluids.

Drug evaluation: Albuferon-alpha--an antiviral interferon-alpha/albumin fusion protein.

Human Genome Sciences Inc (HGS), in collaboration with Novartis AG, is developing Albuferon-alpha, a long-acting injectable human interferon alpha2b fusion protein, for the potential treatment of hepatitis C virus (HCV) infection. By May 2004, phase II clinical trials of Albuferon in HCV infection were underway. In June 2006, HGS planned to initiate phase III clinical trials in this indication by the end of 2006. Albuferon also has the potential to treat a broad range of cancers.

[Clinical study on severe acute pancreatitis associated with hypoalbuminemia in early stage].

OBJECTIVE: To investigate the occurring mechanism and clinical characteristics of severe acute pancreatitis (SAP) associated with hypoalbuminemia in early stage and its influence on prognosis of SAP and the preventive and therapeutic management of this disease. METHODS: One hundred and thirty-eight cases diagnosed as SAP complicated by hypoalbuminemia in early stage were accepted in our hospital from August 1, 2003 to December 31, 2004, and they were divided into 2 groups according to the level of plasma albumin: mild hypoalbuminemia (30 to 35 g/L) group and severe hypoalbuminemia (<30 g/L) group. The complications in the early stage, related parameters, and the incidence rate of infection and mortality in the later stage were evaluated respectively. RESULTS: The incidence rates of renal dysfunction, shock, cardiovascular failure and gastrointestinal hemorrhage, the score of acute physiology and chronic health evaluation II (APACHE II ) and the frequencies of pulse and breath in the severe hypoalbuminemia group were all higher than those in the mild hypoalbuminemia group (P<0.05 or P<0.01). The differences of incidence rate of hepatic failure and the scores of Ranson and Balthazar CT between these two groups had no statistical significance (P>0.05). The incidence rate of infection and the mortality in the severe hypoalbuminemia group were higher than those in the mild hypoalbuminemia group (P<0.01) in the later stage of SAP. CONCLUSION: Hypoalbuminemia in the early stage can accelerate the deterioration in pathophysiology of SAP. The lower level of the plasma albumin is in the early stage, the more complications and the higher incidence rate of infection and mortality will be in the later stage. To relieve the extent of systemic inflammatory response syndrome (SIRS) and abundant supplement of albumin, amino acid and lipid in time may be crucial to prevent the occurrence and deterioration of hypoalbuminemia.

Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection.

BACKGROUND AND PURPOSE: High-dose human albumin therapy is strongly neuroprotective in models of brain ischemia and trauma and is currently being studied in a pilot-phase clinical stroke trial. Among its actions in ischemia, albumin induces the systemic mobilization of n-3 polyunsaturated fatty acids and may help to replenish polyunsaturated fatty acids lost from neural membranes. METHODS: We complexed 25% human albumin to docosahexaenoic acid (DHA; 22:6n-3) and compared its neuroprotective efficacy with that of native albumin in rats with 2-hour focal ischemia produced by intraluminal suture-occlusion of the middle cerebral artery. RESULTS: In animals treated with DHA-albumin, 0.63 g/kg, the improvement in neurobehavioral scores at 72 hours significantly exceeded that of other treatment groups, and the extent of histological protection (86% reduction in cortical infarction) was highly significant and tended to surpass the degree of cortical protection produced by native albumin at 1.25 g/kg (65%). DHA-albumin 0.63 g/kg, but not native albumin, also significantly reduced subcortical infarction and markedly diminished brain swelling. Lipidomic analysis of DHA-albumin-treated postischemic brains revealed a large accumulation of the neuroprotective DHA metabolite, 10,17S-docosatriene, in the ipsilateral hemisphere. CONCLUSIONS: The high-grade neuroprotection afforded by the DHA-albumin complex at relatively low albumin doses is clinically advantageous in that it might reduce the likelihood of acute intravascular volume overload and congestive heart failure sometimes induced when patients with compromised cardiovascular function are treated with high-dose albumin.

Hemodilution with stroma-free [correction of stoma-free] hemoglobin at physiologically maintained viscosity delays the onset of vasoconstriction.

Solutions of modified cell-free hemoglobin, prepared from outdated red blood cells, have been developed during the past decade to circumvent the increasing need for allogeneic blood. Despite improvements in the safety and efficacy of these solutions, undesirable effects such as an increase in vascular tone leading to hypertension have not been fully resolved, which might hinder their clinical usefulness. To discriminate between the pharmacological and rheological effects of cell-free hemoglobin, we compared the effects of blood/cell-free hemoglobin mixtures of high versus low viscosity on hemodynamics and vascular hindrance, an index of vascular tone, which was normalized for blood viscosity. Anesthetized rats were subjected to 50% exchange transfusion with (1) high-viscosity solutions: whole blood (n=5) or red blood cells mixed with cell-free hemoglobin (Hb-Hv group, n=5); (2) low-viscosity solutions: cell-free hemoglobin (Hb-Lv group, n=5) or human albumin (n=5). Two hours after hemodilution, vascular hindrance remained unchanged in animals transfused with whole blood and albumin. Hb-Lv induced an immediate and sustained increase in vascular hindrance (208%). Conversely, in Hb-Hv animals, the vascular hindrance increase was delayed and smaller (27% to 147%), whereas peripheral resistance increased gradually (94% after 2 hours). Our results demonstrate the beneficial effects of cell-free hemoglobin in the presence of the animals' own red blood cells in maintaining physiological viscosity and limiting vasoconstriction because of the pharmacological properties of cell-free hemoglobin.

Ionized calcium changes during living-donor liver transplantation in patients with and without administration of blood-bank products.

Exogenous citrate load from blood transfusion during orthotopic liver transplantation is thought to be the main cause of ionized hypocalcemia, which may result in hemodynamic instability. This implies that if no blood is transfused, chelation of free ionized calcium (Ca(++)) by citrate is avoided and supplemental calcium need not be given. For this study, we divided 39 pediatric living-donor liver transplant patients into two groups according to the blood component replacement given: group I received packed red blood cells and fresh frozen plasma with and without 5% albumin, and group II received 5% albumin alone. The intra-operative serial ionized calcium level was recorded, and the amount of calcium chloride replacement to maintain acceptable blood Ca(++) levels was compared between the groups. The mean serum ionized calcium level changes of both groups could be maintained within lower-to-normal limits intra-operatively. The amount of supplemental calcium chloride required to correct the hypo-ionized calcium was not significantly different between the groups. We can conclude that if an exogenous citrate load is eliminated by the avoidance of blood transfusion and 5% albumin infusion is used, instead, to replace the blood and ascites loss during OLT, the risk of ionic hypocalcemia still persists. Serum Ca(++) monitoring and adequate replacement are, therefore, still required in this setting.

Systemic fatty acid responses to transient focal cerebral ischemia: influence of neuroprotectant therapy with human albumin.

Human albumin therapy is highly neuroprotective in focal cerebral ischemia. Because albumin is the main carrier of free fatty acids (FFA) in plasma, we investigated the content and composition of plasma FFA in jugular vein (JV), femoral artery (FA) and femoral vein (FV) of rats given intravenous human albumin (1.25 g/kg) or saline vehicle (5 mL/kg) 1 h after a 2 h middle cerebral artery occlusion (MCAo) or sham surgery. Arachidonic acid was the only FFA significantly increased by MCAo in all plasma samples prior to albumin administration, remaining at the same level regardless of subsequent treatments. Albumin treatment induced in both MCAo- and sham-groups a 1.7-fold increase in total plasma FFA (mainly 16:0, 18:1, 18:2n-6) during 90-min reperfusion. MCAo selectively stimulated the albumin-mediated mobilization of n-3 polyunsaturated fatty acids (PUFA), with an early increase in 22:5n-3 and 22:6n-3 in the FA prior to detectable changes in the JV. In the MCAo-albumin group, the lower level of FFA in JV as compared with FA and FV suggests an albumin-mediated systemic mobilization and supply of FFA to the brain, which may favor the replenishment of PUFA lost from cellular membranes during ischemia and/or to serve as an alternative source of energy, thus contributing to albumin neuroprotection.

Follow-up study of auditory brainstem responses in infants with high unbound bilirubin levels treated with albumin infusion therapy.

BACKGROUND: Several authors reported that there was a close relationship between unbound bilirubin concentrations and abnormal results of auditory brainstem responses. Full-term infants with high-unbound bilirubin concentrations who were treated with human albumin were followed to evaluate their hearing abilities by using auditory brainstem responses. METHODS: Fifty-eight infants (gestational age, 39.4 +/- 1.4 weeks; birthweight, 3,245 +/- 435 g) with high unbound bilirubin concentrations (> or = 0.9 micro g/dL) were treated with intensive phototherapy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given i.v. human albumin administration (1 g/kg bodyweight) during the first 2 h of phototherapy. The follow-up study of auditory brainstem responses was carried out at 6 and 12 months of age. Development quotient tests were carried out at 18 months of age. RESULTS: Abnormalities of auditory brainstem response were detected in three infants in the albumin-treated group and six infants in the control group at 6 months. Two infants in the albumin-treated group and four infants in the control group had improved at 12 months. The results of the follow-up study at 18 months of age in the both groups were normal with development quotient >85. No patients with hearing disability and cerebral palsy were clinically detected at the age of 2 years. CONCLUSION: The results suggest that albumin priming might be effective for decreasing the rate of auditory brainstem response abnormalities at 6 months.

Use of autologous blood as part of the perfusate for cardiopulmonary bypass: a priming technique.

In an attempt to replace the oncotic and protein coating capabilities of serum albumin in the perfusate, we established a priming protocol that used autologous blood as part of the perfusate solution. Prior to March 1, 1999, our standard priming protocol was 1650 ml of crystalloid with 250 ml of 5% serum albumin and 5,000 units of heparin. After removing albumin from our prime, our standard protocol was altered to include 40 ml of the patient's autologous blood in 1,800 ml of crystalloid and 10,000 units of heparin. To determine the intraoperative effects of using albumin/crystalloid primes (Group A), autologous blood/crystalloid primes (Group B) and crystalloid primes (Group C), a total of 178 patients were sequentially evaluated. Intraoperative parameters evaluated were total protein (TP), colloid osmotic pressure (COP), platelets (Plts) and fluid requirements during cardiopulmonary bypass (CPB). During an overlapping 12-month period of time, 1,092 consecutive cardiac surgical cases using CPB (584 albumin prime; 508 autologous blood prime) were evaluated for clinical outcomes in terms of mortality and length of hospitalization. In addition, over a period of 15 months, 1,458 patients in both the autologous blood/crystalloid group and the crystalloid only group were evaluated for the incidence of high-pressure excursions (HPE) after going on bypass. Comparative reviews of TP, COP and Plts demonstrated no significant difference 10 min after the start of bypass between Groups A and B. However, in Group C, there was a statistically significant increase in the intraoperative fluid requirements during CPB, compared to both of the other groups. There was no significant difference in the incidence of HPE, with an occurrence of 1.04% in the crystalloid only group and 1.11% in the autologous blood/crystalloid group. Autologous blood perfusates were identical to albumin perfusates in their platelet protection and reduction of fluid shifts during the intraoperative period.