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Background: The storage of red blood cells (RBC) is associated with impairment of their properties that can induce a circulatory risk to recipients. In a preceding study (2009), we reported that post-storage rejuvenation (RJ) of stored RBC (St-RBC) efficiently reduced the storage-induced RBC/endothelial cell interaction, while only partially reversing the level of intracellular Ca(2+), reactive oxygen species, and surface phosphatidylserine. In the present study, we examined the RJ effectiveness in repairing St-RBC mechanical properties., Methods: RBC, stored in CPDA-1 without pre-storage leukoreduction, were subjected to post-storage RJ, and the deformability, osmotic fragility (OF), and mechanical fragility (MF) of the rejuvenated St-RBC (St-RBCRj) were compared to those of untreated St-RBC and of freshly-collected RBC (F-RBC)., Results: 5-week storage considerably increased OF and MF, and reduced the deformability of St-RBC. All alterations were only partially (40-70%) reversed by RJ, depending on the extent of the damage: the greater the damage, the lesser the relative effect of RJ., Conclusion: The findings of the present and preceding studies suggest that different St-RBC properties are differentially reversed by RJ, implying that some of the changes occur during storage and are irreversible.

Many psychological disorders comprise a seasonal component. For instance, seasonal affective disorder (SAD) is characterized by depression during autumn and winter. Because hippocampal atrophy may underlie the symptoms of depression and depressive-like behaviors, one goal of this study was to determine whether short days also induce structural changes in the hippocampus using photoperiod responsive rodents--Siberian hamsters. Exposure to short days increases depressive-like responses (increased immobility in the forced swim test) in hamsters. Male hamsters were housed in either short (LD 8:16) or long days (LD 16:8) for 10 weeks and tested in the forced swim test. Brains were removed and processed for Golgi impregnation. HPA axis function may account for photoperiod-related changes in depressive-like responses. Thus, stress reactivity was assessed in another cohort of photoperiod-manipulated animals. Short days reduced soma size and dendritic complexity in the CA1 region. Photoperiod did not induce gross changes in stress reactivity, but an acute stressor disrupted the typical nocturnal peak in cortisol concentrations. These data reveal that immobility induced by exposure to short days is correlated with reduced CA1 cell complexity (and perhaps connectivity). This study is the first to investigate hippocampal changes in the context of short-day induced immobility and may be relevant for understanding psychological disorders with a seasonal component., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Red blood cell (RBC) flow properties (FPs), specifically their deformability, aggregability, and adherence to endothelial cells, play major roles in blood circulation. Their impairment, as occurs under various blood banking conditions, may contribute to circulatory impairment in recipients. Recent studies and meta-analyses show that the transfusion of stored RBCs (stRBCs) may be less beneficial than that of freshly collected units, which may thus adversely affect recipients, especially their circulatory function, thereby pointing to a potential role in the alteration of FPs of stRBCs. In this review, we present an up-to-date summary of the studies on the FP of stRBCs, clearly showing that they may be impaired at an early stage of storage, which may contribute considerably to transfusion-associated circulatory impairment in recipients. The alteration of the FPs of stRBC is attenuated by prestorage leukoreduction and/or poststorage "rejuvenation." However, because these procedures, especially rejuvenation, are costly and are associated with an increased risk of bacterial contamination, there is an urgent need to establish better methods of improving the hemodynamic function of stRBCs before their transfusion. It is therefore proposed that the FPs of stRBC may be important measures of the outcome of RBC transfusions. Monitoring such functions would thereby introduce necessary criteria and new tools for the quality control of stRBC units, making an important contribution to transfusion therapy., (Copyright © 2011. Published by Elsevier Inc.)

Background: Blood banking procedures are associated with elevated adherence of red blood cells (RBCs) to blood vessel wall endothelial cells (ECs), which can introduce a circulatory risk to recipients. This study was undertaken to examine the possibility of repairing this damage by a poststorage "rejuvenation" procedure before transfusion., Study Design and Methods: Stored RBCs were treated with rejuvenation solution (Rejuvesol, enCyte Systems, Inc.), and their adhesion to cultured human microvascular ECs was determined as a function of shear stress using a cell flow properties analyzer. The adherence of rejuvenation-treated stored RBCs (stRBCs) was compared to that of untreated stRBCs and of freshly donated RBCs., Results: Strong elevation of stRBC/EC adhesion was induced by cold storage and it correlated with translocation of phosphatidylserine (PS) to the RBC surface, a known mediator of RBC/EC adhesion. The role of RBC surface PS in stRBC/EC interaction was confirmed by the suppression of adhesion after the blocking of the stRBC surface PS with annexin V. Concomitantly, RBC storage elevated intracellular levels of reactive oxygen species (ROS) and Ca(2+), the latter known to facilitate PS externalization. Poststorage rejuvenation treatment of stRBCs reversed all the above changes (ROS, Ca(2+), PS), along with complete suppression of the enhanced RBC/EC adhesion, restoring it to that of normal, freshly collected RBCs., Conclusion: Poststorage RBC rejuvenation treatment is effective in reversing the storage-induced RBC/EC interaction. This provides further documentation for the potential clinical benefit of poststorage rejuvenation.

Background: Blood banking procedures are associated with damage to red blood cell (RBC) membranes, which can impair their flow properties, namely, their deformability, aggregability, and adherence to endothelial cells (ECs) and thus possibly introducing a circulatory risk to recipients. This study was undertaken to comprehensively explore the effect of cold storage and gamma irradiation on RBC flow properties., Study Design and Methods: RBC flow properties were monitored as a function of shear stress with a computerized cell flow properties analyzer. Because we had previously studied storage effect on RBC aggregability (Transfusion 1999;39:277-81), here we determined the storage effect on RBC adherence and deformability, by measuring them before (control) and during storage. Gamma irradiation effect on RBC aggregability, adherence, and deformability was determined before (control) and after irradiation., Results: Cold storage significantly elevated the number of adherent RBCs and the strength of their interaction with ECs, and was marked by decreased RBC deformability as early as 2 weeks into the storage period. The elevation of RBC-EC interaction was well correlated with translocation of phosphatidylserine to the RBC surface. Gamma irradiation induced an immediate and marked increase in the number of rigid cells, but did not affect RBC adherence and aggregability., Conclusion: RBC flow properties appear to be especially sensitive to cold storage and gamma irradiation because they are impaired long before the expiration date. Because impaired RBC flow properties facilitate circulatory disorders, the potential circulatory risk of transfusion RBC with blood banking-impaired rheology should be considered.

Dual or multiple cell populations, induced by chimeras, have been the subject of many studies. This long-standing fascination with chimeras has revealed a good deal of knowledge about human inheritance. Although historically most chimeras were caused by natural events, certain current medical intervention therapies are increasing the number of situations that can lead to a mixed cell population, that is, the chimeric condition, in humans. Medical therapies such as transfusion, stem cell transplantation, kidney transplantation, and artificial insemination induce temporary and sometimes permanent chimeras. Such natural or therapeutically induced presentations of chimerism can present challenging issues to the clinical immunohematology laboratory with regard to interpretation of results and subsequent patient management. The purpose of this review was to highlight some of these chimeric states and hypothesize how testing DNA from various tissues can cause apparent discrepancies between phenotype and genotype results.

Background: Lu6 is a high-incidence antigen of the Lutheran blood group. Examples of anti-Lu6 are rare and are of uncertain clinical significance., Case Report: Three patients were encountered in whom anti-Lu6 was detected on pretransfusion screening. The patients were all Iranian Jews and were not known to be related. In vitro studies to ascertain the potential clinical significance of the antibody using the monocyte monolayer assay (MMA) were negative in two patients. The third patient received a two-unit transfusion of incompatible Lu6 RBCs with no signs of hemolysis. However, after the transfusion, the MMA and a chemiluminescence test were positive, whereas a chromium survival study was normal. Thus, the antibody may have changed in its clinical significance., Conclusion: Although anti-Lu6 does not appear to be a clinically significant RBC antibody in all circumstances, transfusion of Lu6 RBCs in patients with anti-Lu6 should be performed cautiously.

Objective: To assess whether hospital work constitutes a risk factor for hepatitis C virus (HCV) infection among employees of a large hospital in Israel., Design: Seroprevalence survey., Setting: A 1,006-bed, tertiary-care university hospital in Jerusalem., Participants: All 5,444 employees (18-65 years old) were eligible; 4,287 (79%) participated in the survey., Methods: Sera were tested for antibodies to HCV (anti-HCV) using a third-generation enzyme immunoassay. A third-generation strip immunoblot assay was used for confirmation. Participants were interviewed regarding their occupational history, and they completed a self-administered questionnaire covering history of non-occupational exposure to blood and country of birth. Other demographic information was obtained from the personnel department. Rates and odds ratios (ORs) were calculated, and multivariate logistic-regression analyses were performed to adjust for potential confounding variables., Results: Anti-HCV was found in 0.9% of employees (37/4,287; 95% confidence interval, 0.6-1.1), ranging from 0.1% among those born in Israel to 5.7% among those born in Central Asia. After age, gender, social status, country of birth, and history of blood transfusion were controlled for in a logistic regression, occupational exposure to blood > or = 10 years was significantly associated with the presence of antibodies (OR, 2.6; P=.01). Presence of anti-HCV also was associated with country of birth (range: Israel OR, 1; West OR, 3.8 [P=.1]; Central Asia OR, 48.6 [P<.0001]) and history of blood transfusion (OR, 2.7; P=.01). No significant associations were found between anti-HCV and age, gender, social status, history of tattoo, acupuncture, current occupation, department, exposure to blood in current occupation, adherence to safety precautions, or history of percutaneous injury. The association with length of exposure was stronger (OR, 3.6; P=.01) when the same logistic regression was run excluding the outlier ethnic group of Central Asia., Conclusions: Hospital work does not seem to constitute a major risk factor for HCV infection in Israel today. A higher prevalence of anti-HCV among employees with longer versus shorter lengths of occupational exposure may be due to a cumulative effect of exposure over the years. Infection control efforts in recent years may have contributed to this association.

Objective: An Rh-negative woman with preexisting anti-D antibodies may affect some or all subsequent fetuses, depending on the genotype of her Rh-positive partner. Currently, a reliable technique for an absolute determination of RhD genotype is not available. This study was initiated to develop an accurate method for RhD genotyping in men., Study Design: RhD genotype was determined by deoxyribonucleic acid amplification of a D-specific sequence in single sperm cell samples. Micromanipulation techniques were used for sampling of single sperm cells, which were further amplified by multiplex nested polymerase chain reaction at the RhD locus. A RhD sequence amplification product was expected in all of the successfully amplified samples from Rh-positive homozygotes, in some of the samples from heterozygotes, and in none of the samples form Rh-negative subjects., Results: RhD genotype was accurately determined in 10 of 10 donors. A total of 132 single sperm cells were analyzed (8 to 17 samples per donor), of which 96 were successfully amplified as assessed by an internal control. As expected, the specific region of the RhD gene was amplified in all, some, and none of the signal-positive sperm samples from Rh-positive homozygotes, heterozygotes, and Rh-negative subjects, respectively, allowing accurate determination of the genotype., Conclusion: An accurate diagnosis of the RhD genotype can be attained from single sperm cell analysis by means of polymerase chain reaction and may have major clinical applications in the management of Rh isoimmunization.

Although full blood counts (FBC) are among the most commonly performed laboratory tests, the contribution of routine FBCs to the diagnosis of new problems is controversial. This study represents a unique linkage of a consultant haematology team, reviewing all abnormal blood counts, to an organization providing ambulatory health care to 350,000 patients. The objective was to establish the underlying clinical disorders responsible for all abnormal FBCs during a 2-month period, and to estimate the impact of the haematology team on the diagnostic work-up and management of newly identified problems. 572 (2.55%) of the 22,454 FBCs were abnormal. Of these, 357 showed microcytosis, caused by iron deficiency (58%), thalassaemia minor (35%), inflammation (6%) or chronic renal failure (1%). The most common causes of normocytic anaemia (25 patients) were disseminated malignancy and acute blood loss; of macrocytosis (27 patients), chronic liver disease and cancer; of erythrocytosis (16 patients), chronic hypoxia; of thrombocytopaenia (48 patients), chronic liver disease and ITP; of thrombocytosis (47 patients), iron deficiency and inflammation; of leukopaenia or pancytopaenia (20 patients), cirrhosis and disseminated malignancy; and of leukocytosis (26 patients), chronic leukaemias in the elderly and infection in children. Major new haematological abnormalities were encountered in 0.24% of all blood counts, representing about one new diagnosis per day. Routine blood counts do contribute to the health care of a population. Screening for haematological disease through a central clinical laboratory covering a large high-risk ambulatory population offers a cost-effective way of searching for serious clinical problems, alerting the primary physicians of their existence, and offering advice in continued evaluation and problem management.

In order to study the asymptomatic hepatitis C virus (HCV)-positive blood donors in Israel we analyzed their sera for HCV-RNA using the polymerase chain reaction technique. We found that 0.44% of blood donors were anti-HCV positive. Of those who had repeatedly positive anti-HCV, 82% had evidence of HCV-RNA. One-third of them had elevated liver enzymes, but no detectable cryoglobulins were found in their sera. Although HCV-RNA was detected in the majority of the patients, we were unable to demonstrate vertical or horizontal transmission among the family members of our carrier population.

We studied 24 HIV-positive Palestinians who presented for medical care in the West Bank, Jerusalem and the Gaza Strip between 1987 and 1992. Three individuals, all males, were detected by blood bank screening. An additional 21 individuals (12 males, 7 females, 2 infants) were diagnosed as having HIV infection. Fifteen of 24 had full-blown AIDS--11/24 (46%) were expatriates; there were 4 heterosexuals, 5 transfusion recipients and 6 homosexuals, together comprising 79% of the individuals whose risk group was known. As compared with Israelis, Palestinians presented for medical treatment at a later stage of HIV infection. We also studied the incidence of HIV infection among Palestinian blood donors between 1987 and 1992. The incidence analysis was based on HIV screening at seven blood banks of major hospitals in the West Bank, at the Makassed Hospital in East Jerusalem, at Hadassah University Hospital (Palestinian blood donors only) and at two blood banks in the Gaza Strip. Demographic features were derived from the health department of the West Bank and from the AIDS clinic at Hadassah Hospital. Approximately 50,000 Palestinians were screened at the blood banks. Only three, all males, were detected as HIV seropositive, giving an HIV overall cumulative incidence of 0.006%. This figure was similar to the incidence among 500,000 Israeli donors (0.008%; NS) during that period. Although the low HIV incidence at the blood banks is encouraging, the negligible number of HIV seropositives and the presentation at a late clinical stage points to a deficiency in AIDS tracing and in access to specialized AIDS care in the West Bank and the Gaza Strip. The small overall number of cases precludes any definite conclusion as to trends in the epidemiology of AIDS in the West Bank and Gaza. However, the receipt of contaminated transfusions and the return of infected expatriates seem to be important features of AIDS in the West Bank and Gaza.

Leukocyte antibodies are the major cause of nonhemolytic transfusion reactions. One of the less frequent but severe forms of this reaction is the adult respiratory distress syndrome, or transfusion-related acute lung injury. This rare phenomenon is the result of leukocyte antibodies forming immune complexes with granulocytes, complement activation, sequestration of activated granulocytes in the pulmonary capillary bed, and their degranulation associated with release of proteolytic and cytotoxic substances. This cascade causes endothelial damage with increased capillary permeability. Plasma fluids and proteins accumulate in the interstitial and intra-alveolar spaces, leading to respiratory insufficiency. We present two patients with transfusion-related adult respiratory distress syndrome associated with leukocyte HLA antibodies, who were successfully treated in our hospital. The pathogenesis, diagnostic measures and treatment of this uncommon yet critical condition is discussed.

To test the hypothesis that transfusion of blood donated by individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may result in a hemolytic reaction, we conducted a prospective longitudinal study in which 10 patients transfused with 1 unit of G6PD-deficient and 1 unit of normal red blood cells (RBC) were compared with 10 patients transfused with 2 units of age-matched normal RBC. We found that 24 h after transfusion serum bilirubin (mumol/l) in the recipients of G6PD-deficient RBC was significantly higher than in the recipients of normal RBC (36 +/- 14 vs. 18 +/- 5, respectively, p > 0.004). A parallel increase was found in the serum lactate dehydrogenase (LDH; IU/l) between the two groups (378 +/- 151 vs. 264 +/- 56, p < 0.001). The difference in serum bilirubin (26 +/- 10 vs. 15 +/- 5, p < 0.03) was still noted 48 h after transfusion, with only a marginal difference (p < 0.08) in LDH. We conclude that an immediate posttransfusional hemolytic reaction can occur in recipients of G6PD-deficient RBC and therefore suggest that the differential diagnosis of posttransfusional hemolysis, particularly in populations where G6PD deficiency is prevalent, includes transfusion of erythrocytes from G6PD-deficient donors.

In 15 patients undergoing aortofemoral bypass, partial thromboplastin time (PTT) tests before and following intravenous administration of 75 U. per kilogram of heparin at zero, 30, 60, 90, and 120 minutes were determined for study of control of anticoagulant adequacy. The results demonstrate clearly that this amount provides excellent protection against thrombosis without bleeding complications. For intraoperative assay of heparin level effectiveness, the PTT test is advised. This test showed that a value of 250 percent of control still existed 75 minutes following the administration of heparin.

The prevalance of traumatic intravascular hemolysis was estimated in 25 patients following aortofemoral bypass. Stigmata of mild red cell fragmentation were noted in approximately one third of the patients, but in only one of them was hemolysis of sufficient severity to be of clinical significance. The case history and laboratory findings in this patient are described in detail. This study indicates that traumatic hemolysis should be considered as a possible cause of anemia developing after aortofemoral bypass.

An analysis of the etiology of acute viral hepatitis in 172 hospitalized patients showed that 70.9% suffered from hepatitis A (HA), 12.2% from hepatitis B (HB), 1.7% from infectious mononucleosis and 15.1% (26 cases) from non-A, non-B hepatitis. Patients who had received blood transfusions during the 6 mo preceding the onset of the disease were not included in the present survey. The male:female ratio in the patients with non-A, non-B hepatitis was 1:88; 73% were Ashkenazic and 27% non-Ashkenazic Jews. The ethnic distribution of patients with non-A, non-B hepatitis was similar to that of patients with HA but differed from that of HB patients (only 41% Ashkenazic). Thirty-eight percent of the non-A, non-B group had had contact with jaundiced patients during the 6 mo preceding the onset of the disease, and 46% were students or soldiers. The clinical course of the disease was, on the whole, milder than that of HB and similar to that of HA. Since many cases of non-A, non-B hepatitis are anicteric, it is concluded that the disease is a significant problem in Israel.

In a prospective study of 50 recipients of HBsAg-negative blood who had undergone cardiac surgery, 4 (8%) developed acute non-A, non-B hepatitis. The patients who developed hepatitis had received significantly more units of blood or blood products than the patients who had no hepatitis. The incubation period of the disease was 4-13 weeks, 3 patients were asymptomatic with peak alaminotransferase (ALT) levels of 320-497 U/1 and 1 patient was jaundiced with a peak ALT of 3,400 U/1. 1 of the patients had high ALT levels after 21 weeks of observation, while 3 patients recovered after 7-10 weeks. It is concluded that non-A, non-B posttransfusion hepatitis in Israel is a medical problem similar to that in the USA and that the clinical picture of the disease varies from a mild asymptomatic to a symptomatic and protracted course.

Several blood constituents were used to evaluate the nutritional status of a random, consecutive group of 655 blood donors. The population included 503 men and 152 women, with a mean age of 35.1 years; 26.8% of the women and 26.5% of the men had deficient levels of ascorbic acid; 18.0% of the women an 11.9% of the men had hemoglobin levels below normal. Plasma iron was inadequate in 29.3% of the women and 18.6% of the men. A very small number of donors were found to be deficient in carotene, retinol, thiamine, riboflavin and pyridoxine. These findings call attention to an unexpected aspect of nutrition in an apparently healthy, not undernourished population.

The unsaturated B12 binding capacity (UBBC) of the serum and the binding capacity of each of the 3 vitamin B12 binders--the transcobalamins (TC) I, II and III were determined in 21 patients with polycythaemia vera (PV) during the course of the disease and following treatment, using the recently described charged cellulose filter technique. High serum UBBC due to elevated serum TCIII was found in all patients. TCI was moderately elevated in patients who had leucocytosis with a shift to the left. The changes in serum TCIII and UBBC correlated with the activity of the disease. Chemotherapy resulted in a decrease in TCIII and UBBC. The decrease in TCIII and UBBC folowing chemotherapy may be observed before a decrease in the haematocrit and the leucocyte count occurs. Activation of the disease may be assessed by the elevation of TCIII and UBBC. The onset of acute myeloblastic crisis in 1 patient was associated with a decrease in TCIII and TCI levels and a rise in serum TCII. The determination of TCIII and UBBC may be helpful in differentiating true from secondary polycythaemia.

Monoclonal anti GP-70 antibodies (BI) were generated in mice and used for screening of various malignant and non-malignant cell lines. The reactivity of these monoclonal antibodies was compared with that obtained with the polyclonal anti GP-70 antibody described in earlier studies [1-3]. The results indicated complete similarity in reactivity of both of the antibodies used. Furthermore, the reactivity of BI antibodies with cell samples obtained from a variety of leukemia and lymphoma patients and with peripheral blood samples from healthy blood donors was also very similar to the pattern of specificity described in earlier reports for the polyclonal preparation. From these studies we conclude that the monoclonal antibodies can substitute the polyclonal anti GP-70 antibodies in the diagnosis and subtyping of B-type leukemias and lymphomas.

Acid aspiration may recruit a generalized inflammatory reaction that can potentiate the local injury. After surgical isolation of bronchi in a group of 15 dogs, 1 milliliter per kilogram of 0.37 normal hydrochloric acid was instilled into either side. After five minutes, platelet and white blood cell counts fell to 10,000 and 1,000 per cubic millimeter (p less than 0.05). Platelet aggregates were noted in blood smears. 111Indium-platelet activity doubled over both the aspirated and nonaspirated lung (p less than 0.05). Physiologic dead space rose from 18 to 67 per cent and to 46 per cent in the aspirated and nonaspirated lung (p less than 0.05). Physiologic shunt increased from 12 to 47 per cent and to 43 per cent (p less than 0.05) on the two sides. Plasma thromboxane B2 levels at 30 minutes rose from 0.28 to 0.93 nanograms per milliliter (p less than 0.05). Edema fluid from the aspirated lung had thromboxane B2 values of 2.87 nanograms per milliliter, indicating pulmonary synthesis. Within five minutes of aspiration, systemic effects were prominent; mean arterial pressure fell from 114 to 46 milliliters of mercury (p less than 0.05), and the cardiac index fell 24 per cent from 106 to 81 milliliters per kilogram per minute (p less than 0.05) along with an 18 per cent decrease in contractility of a rat papillary muscle bathed in plasma from the aspirated dog. Mean pulmonary arterial pressure rose from 12 to 18 millimeters of mercury (p less than 0.05). Despite fluid infusion at 36 milliliters per kilogram per hour to keep wedge pressure constant at 5.5 millimeters of mercury, and sampling of one-third the blood volume, hemoglobin concentration rose 0.9 grams per cent (p less than 0.05) indicating increased microvascular permeability. At autopsy, the aspirated and nonaspirated lung were indistinguishable with congestion, interstitial hemorrhage, and white blood cell infiltrates. Systemic organs showed vascular congestion and edema. These data demonstrate that local aspiration leads to generalized inflammatory sequelae with cardiopulmonary failure.